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Molecular Pathogenesis

Cytokine and Fibrogenic Gene Expression in the Conjunctivas of Subjects from a Gambian Community Where Trachoma Is Endemic

Matthew J. Burton, Robin L. Bailey, David Jeffries, David C. W. Mabey, Martin J. Holland
Matthew J. Burton
1London School of Hygiene and Tropical Medicine, London, United Kingdom
2Medical Research Council Laboratories, Fajara, The Gambia
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  • For correspondence: matthew.burton@lshtm.ac.uk
Robin L. Bailey
1London School of Hygiene and Tropical Medicine, London, United Kingdom
2Medical Research Council Laboratories, Fajara, The Gambia
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David Jeffries
2Medical Research Council Laboratories, Fajara, The Gambia
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David C. W. Mabey
1London School of Hygiene and Tropical Medicine, London, United Kingdom
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Martin J. Holland
1London School of Hygiene and Tropical Medicine, London, United Kingdom
2Medical Research Council Laboratories, Fajara, The Gambia
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DOI: 10.1128/IAI.72.12.7352-7356.2004
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ABSTRACT

The role of immunity in blinding trachoma is unclear. Conjunctival gene expression was measured in a population where trachoma is endemic. Proinflammatory (tumor necrosis factor alpha and interleukin-1β [IL-1β]), anti-inflammatory (IL-10), and fibrogenic (matrix metalloprotease 9) gene expression was increased in active trachoma. Markers indicative of T-cell response (gamma interferon, IL-4, IL-12p40, and perforin) were increased when chlamydial infection was present.

Trachoma is the leading infectious cause of blindness (39). Repeated conjunctival infection with Chlamydia trachomatis drives a progressive process of scarring, trichiasis, and corneal opacification. While the conjunctival immune response is important in resolving infection, immunopathological events may initiate the scarring process (21). Similar scarring occurs in genital C. trachomatis infection, where it leads to infertility and ectopic pregnancy.

Our understanding of which immunological responses promote resolution of human C. trachomatis infection and which promote scarring is currently limited. This needs to be improved if a vaccine capable of inducing protection without risk of tissue damage is to be developed. We studied patterns of conjunctival immunological and fibrogenic responses in a community where trachoma is endemic by measuring mRNA expression, using quantitative reverse transcriptase PCR (RT-PCR), for informative cytokine and fibrogenic factors in relationship to disease and infection.

The study was approved by the Gambian Government/Medical Research Council Joint Ethics Committee. All available residents of two Gambian villages were examined for active trachoma (F2/F3 or P3) by an ophthalmologist (13). Swab samples from the left upper tarsal conjunctival surface were collected into RNALater (Ambion Inc., Austin, Tex.) on ice and stored at −20°C.

Total RNA was extracted with the RNeasy minikit (QIAGEN, Crawley, United Kingdom). C. trachomatis 16S rRNA expression was quantitated in duplicate by a one-step, real-time RT-PCR using the QuantiTect SYBR Green RT-PCR kit (QIAGEN) with previously described primers (Table 1) (22) on an ABI 5700 sequence detection system (Applied Biosystems, Warrington, United Kingdom). Human RNA was reverse transcribed with the Omniscript RT kit (QIAGEN) and oligo-dT15 primers. The expression of human genes (Table 1) was quantitated in duplicate by two-step, real-time RT-PCR with the QuantiTect SYBR Green PCR kit (QIAGEN). A standard calibration curve was generated for each run of the assay. Standards were produced by serial 10-fold dilutions of known amounts of target DNA in ultrapure water with 2 ng of herring sperm DNA/μl. Results are presented as a ratio to the expression of hypoxanthine phosphoribosyl transferase 1 (HPRT-1) in the same sample.

In all, 248 subjects participated (79% of the total population). The median age was 12 years, all were of the Wolof ethnic group, and 59% were female. Clinically active trachoma was diagnosed in 42 subjects (16.9%), and infection (C. trachomatis 16S rRNA expression) was detected in 17 (6.8%) subjects, including 14 with active trachoma.

The mRNA expression of various cytokines and fibrogenic factors (Table 1) was quantitated in all 248 samples. Insufficient sample volume precluded measurement of matrix metalloprotease 9 (MMP-9) and type I collagen in 2 and 42 specimens, respectively. Transforming growth factor β1 (TGF-β1) was assayed in 82 samples and found to be undetectable or present at only very low levels. Data were analyzed for three subject groups by using STATA 7 and Genstat 6.1: group 1, 203 noninfected, clinically normal; group 2, 17 infected; and group 3, 28 noninfected but with active disease. The geometric mean and median values of the various targets by these subdivisions are shown in Table 2.

Comparisons across disease and infection states were made with a linear mixed model (after log10 transformation of the ratios), adjusted for village or compound clustering (random effect) and for gender and age. Targets for which the disease or infection state had a significant effect (at P = 0.05) were compared between groups by using the Wald test (Table 3), adjusted for multiplicity by the Holm method (giving a critical significance level of P = 0.0049).

Active trachoma without C. trachomatis infection was associated with increased expression of the cytokines tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-10; subjects infected with C. trachomatis additionally had increased expression of gamma interferon (IFN-γ), IL-12p40, and perforin (Table 2). IL-2 showed a nonsignificant trend towards increased expression in subjects with infection. IL-4 expression was discrete. Where present, it was found at low levels within a narrow range. IL-4 was detected in 99 of 203 (49%) noninfected, clinically normal subjects, 15 of 17 (88%) infected subjects, and 18 of 28 (64%) noninfected, active disease subjects. Infected individuals had significantly more expression of IL-4 than the normal group (odds ratio, 7.88; 95% confidence interval [CI], 1.76 to 35.3; P = 0.002, Fisher's exact test). The IL-12p35 mRNA component of the IL-12 heterodimer (IL-12p75) is known to be constitutively expressed (9) and accordingly did not vary with disease or infection.

The fibrogenic factors TGF-β2, MMP-1, and type I collagen were readily detected in all samples but did not vary with disease or infection state (Table 2). Active disease and chlamydial infection were associated, however, with significantly increased expression of MMP-9 and a small increase in the type I collagen/MMP-1 ratio (Table 2). MMP-9 expression also increased with increasing severity of inflammation (Table 4).

Canonical variate analysis was used to identify linear combinations of these target ratios that best discriminate the three subgroups by maximizing between-group-to-within-group variability. The 95% confidence regions for the group canonical means demonstrate clear separation between the groups (Fig. 1).

The critical event in the pathogenesis of blinding trachoma is the development of chronic conjunctival inflammation, triggered by C. trachomatis infection. Scarring and trichiasis develop in a minority of individuals, suggesting that variations in susceptibility are important. Severe inflammatory trachoma is associated with increased risk of cicatricial complications later in life (14, 40).

These data indicate that active trachoma is associated with increased expression of the proinflammatory cytokines IL-1β and TNF-α. Other studies have found similar associations (3, 8, 10). IL-1β and TNF-α induce MMP activation, collagen production, and fibroblast activation (23, 38, 46), and their prolonged expression is associated with several chronic inflammatory and fibrotic conditions such as rheumatoid arthritis and pulmonary fibrosis (20). These findings support the view that these are important mediators of inflammation in trachoma, whose continued presence following resolution of infection may contribute to the development of scarring.

We found increased IL-10 expression associated with active trachoma. In contrast, a previous study in trachomatous subjects failed to detect IL-10 (8). The effect of IL-10 in trachoma is unclear; it may limit immune-mediated tissue damage through its anti-inflammatory and immunoregulatory effects (27); however, it could also curtail the effector arm of the cell-mediated immune (CMI) response, allowing C. trachomatis to persist (35, 47). We show elsewhere that polymorphism at the IL-10 locus is associated with risk of scarring, and increased IL-10 mRNA from C. trachomatis antigen stimulated peripheral blood mononuclear cells in subjects with trachomatous scarring (16, 26).

C. trachomatis infection was associated with a cytokine response suggestive of activated CMI with significantly increased expression of IFN-γ, IL-4, IL-12p40, and perforin mRNA. IFN-γ is important in the control of chlamydial infections, through several well-described mechanisms (34). In mice, impairment of IFN-γ resulted in prolonged and disseminated infection (12, 19, 32). Peripheral blood mononuclear cells from a population where trachoma is endemic proliferate and produce IFN-γ in response to chlamydial antigens; these responses were weaker in subjects with trachomatous scarring, suggesting that a poor CMI response might be associated with fibrosis through more prolonged infection episodes (16, 17). Increased IL-2 expression with infection suggests T-cell proliferation and is consistent with a previous study of conjunctival gene expression in trachoma (8). IL-12 from dendritic cells and macrophages links the innate and acquired immune responses, driving the proliferation of IFN-γ-producing TH1 cells. In mice, neutralization of IL-12 is associated with reduced levels of IFN-γ and prolonged C. trachomatis infections (29).

The finding of increased IL-4 expression with infection, albeit at low levels, may indicate the presence of TH0, TH2, or other cells, such as natural killer and mast cells. Although resolution of infection probably requires a CMI response dominated by IFN-γ, this may be counterbalanced by a number of factors, including IL-4. These mixed findings are typical of the blend of TH responses frequently observed in human infectious diseases, in contrast to a more polarized response observed in mice. Animal models do not suggest that IL-4 contributes to the resolution of infection (29, 42), although it is expressed in infected tissue (24).

The expression of perforin was used as a marker for cytotoxic T-cell (CTL) activity. CTLs may have an antichlamydial role by targeting infected conjunctival cells and may help contain conjunctival inflammation through leukocyte apoptosis. In mice, CTLs are found in infected tissue (24) but are not necessary for resolution of infection (25, 30). Conjunctival biopsies from children with active trachoma show both CD4+ and CD8+ cells infiltrating the substantia propria (3). Specific antichlamydial CTL responses were found in peripheral blood from adults without scarring and children recovering from active disease (18).

Understanding the fibrogenic process may be the key to unravelling the pathogenesis of trachoma. MMPs are proteolytic enzymes that regulate the extracellular matrix (ECM) and are implicated in fibrotic disease processes (45). Active trachoma, particularly severe inflammation (inflammatory trachoma), and C. trachomatis infection were associated with increased expression of MMP-9. This enzyme may be central to the pathogenesis of trachomatous scarring. Increased MMP-9 expression and functional activity have been demonstrated in conjunctival biopsies from children with active trachoma (15). Studies indicate that C. trachomatis infection is associated with increased MMP-9 activity (6, 31). MMP-9 is activated by proinflammatory cytokines (23, 36) and may in turn perpetuate the inflammation by proteolytic activation of IL-1β (37). MMP-9 degrades the ECM, rendering the conjunctiva more plastic, facilitating the migration of cells, including fibroblasts. MMP-9 can activate TGF-β (5), which promotes scar tissue deposition (7, 11). TGF-β can increase MMP expression, perpetuating this process (41). Interestingly, postoperative inhibition of MMP activity reduces conjunctival scarring (44).

There are three human isoforms of TGF-β, of which TGF-β2 is predominant in conjunctival tissue (28). We found TGF-β2, but not TGF-β1, was readily detectable in all subjects but did not vary with infection or disease. The regulation of TGF-β is largely posttranscriptional; therefore, this finding does not exclude a role for TGF-β in the pathogenesis of scarring trachoma. In vitro and in vivo studies suggest that TGF-β activity increases in C. trachomatis infection (33, 43).

In advanced trachomatous scarring, a thick band of fibrotic tissue composed mostly of type V collagen replaces the normal stromal tissue (2, 4). In biopsies from children with active trachoma, there is an increase in type I and type III collagen between epithelial cells and in the stroma (1). We found the expression of type I collagen did not vary with active disease or infection; however, the type I collagen/MMP-1 expression ratio was higher in both the presence of infection and disease, which could lead to an increase in the amount of collagen deposited in the conjunctiva.

This study demonstrated that active trachoma was characterized by increased expression of TNF-α, IL-1β, IL-10, and MMP-9. In addition, C. trachomatis infection was also associated with cytokines characteristic of a CMI response: IFN-γ, IL-4, IL-12p40, and perforin. Increased expression of MMP-9 in both disease and infection is of particular interest and may provide a mechanism whereby inflammation and ECM breakdown self-perpetuate in the absence of infection and may therefore have an important role in the development of trachomatous scarring.

FIG. 1.
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FIG. 1.

Canonical means for different infection and disease states (+), with 95% confidence regions (circles).

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TABLE 1.

Sequences of the primers used in this studya

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TABLE 2.

Geometric mean and median values of the ratio of the expression of various targets to HPRT by clinical and infection status

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TABLE 3.

 Comparisons between results for different disease and infection states for various targets by the Wald test (P value)

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TABLE 4.

Geometric mean and median values of MMP-9/HPRT ratio by the degree of papillary inflammation

ACKNOWLEDGMENTS

We thank the residents of the villages participating in this study for their good-humored cooperation.

This work was supported by grants from the Medical Research Council and the Wellcome Trust/Burroughs Wellcome Fund.

FOOTNOTES

    • Received 13 May 2004.
    • Returned for modification 30 June 2004.
    • Accepted 21 August 2004.
  • Copyright © 2004 American Society for Microbiology

REFERENCES

  1. 1.↵
    Abu el-Asrar, A. M., K. Geboes, S. A. Al Kharashi, A. A. Al Mosallam, K. F. Tabbara, A. A. al Rajhi, and L. Missotten. 1998. An immunohistochemical study of collagens in trachoma and vernal keratoconjunctivitis. Eye12:1001-1006.
    OpenUrlCrossRefPubMed
  2. 2.↵
    Abu el-Asrar, A. M., K. Geboes, S. A. Al Kharashi, K. F. Tabbara, and L. Missotten. 1998. Collagen content and types in trachomatous conjunctivitis. Eye12:735-739.
    OpenUrlCrossRefPubMedWeb of Science
  3. 3.↵
    Abu el-Asrar, A. M., K. Geboes, K. F. Tabbara, S. A. Al Kharashi, L. Missotten, and V. Desmet. 1998. Immunopathogenesis of conjunctival scarring in trachoma. Eye12:453-460.
    OpenUrlCrossRefPubMedWeb of Science
  4. 4.↵
    al Rajhi, A. A., A. Hidayat, A. Nasr, and M. al Faran. 1993. The histopathology and the mechanism of entropion in patients with trachoma. Ophthalmology100:1293-1296.
    OpenUrlPubMed
  5. 5.↵
    Annes, J. P., J. S. Munger, and D. B. Rifkin. 2003. Making sense of latent TGFbeta activation. J. Cell Sci.116:217-224.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    Ault, K. A., K. A. Kelly, P. E. Ruther, A. A. Izzo, L. S. Izzo, I. M. Sigar, and K. H. Ramsey. 2002. Chlamydia trachomatis enhances the expression of matrix metalloproteinases in an in vitro model of the human fallopian tube infection. Am. J. Obstet. Gynecol.187:1377-1383.
    OpenUrlCrossRefPubMedWeb of Science
  7. 7.↵
    Blobe, G. C., W. P. Schiemann, and H. F. Lodish. 2000. Role of transforming growth factor beta in human disease. N. Engl. J. Med.342:1350-1358.
    OpenUrlCrossRefPubMedWeb of Science
  8. 8.↵
    Bobo, L., N. Novak, H. Mkocha, S. Vitale, S. West, and T. C. Quinn. 1996. Evidence for a predominant proinflammatory conjunctival cytokine response in individuals with trachoma. Infect. Immun.64:3273-3279.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    Cassatella, M. A., L. Meda, S. Gasperini, A. D'Andrea, X. Ma, and G. Trinchieri. 1995. Interleukin-12 production by human polymorphonuclear leukocytes. Eur. J. Immunol.25:1-5.
    OpenUrlCrossRefPubMedWeb of Science
  10. 10.↵
    Conway, D. J., M. J. Holland, R. L. Bailey, A. E. Campbell, O. S. M. Mahdi, R. Jennings, E. Mbena, and D. C. W. Mabey. 1997. Scarring trachoma is associated with polymorphism in the tumor necrosis factor alpha (TNF-α) gene promoter and with elevated TNF-α levels in tear fluid. Infect. Immun.65:1003-1006.
    OpenUrlAbstract/FREE Full Text
  11. 11.↵
    Cordeiro, M. F., M. B. Reichel, J. A. Gay, F. D'Esposita, R. A. Alexander, and P. T. Khaw. 1999. Transforming growth factor-beta1, -beta2, and -beta3 in vivo: effects on normal and mitomycin C-modulated conjunctival scarring. Investig. Ophthalmol. Vis. Sci.40:1975-1982.
    OpenUrlAbstract/FREE Full Text
  12. 12.↵
    Cotter, T. W., K. H. Ramsey, G. S. Miranpuri, C. E. Poulsen, and G. I. Byrne. 1997. Dissemination of Chlamydia trachomatis chronic genital tract infection in gamma interferon gene knockout mice. Infect. Immun.65:2145-2152.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    Dawson, C. R., B. R. Jones, and M. L. Tarizzo. 1981. Guide to trachoma control. World Health Organization, Geneva, Switzerland.
  14. 14.↵
    Dawson, C. R., R. Marx, T. Daghfous, R. Juster, and J. Schachter. 1990. What clinical signs are critical in evaluating the intervention in trachoma?, p. 271-278. In W. R. Bowie (ed.), Chlamydial infections. Cambridge University Press, Cambridge, United Kingdom.
  15. 15.↵
    El Asrar, A. M., K. Geboes, S. A. Al Kharashi, A. A. Al Mosallam, L. Missotten, L. Paemen, and G. Opdenakker. 2000. Expression of gelatinase B in trachomatous conjunctivitis. Br. J. Ophthalmol.84:85-91.
    OpenUrlAbstract/FREE Full Text
  16. 16.↵
    Holland, M. J., R. L. Bailey, D. J. Conway, F. Culley, G. Miranpuri, G. I. Byrne, H. C. Whittle, and D. C. Mabey. 1996. T helper type-1 (Th1)/Th2 profiles of peripheral blood mononuclear cells (PBMC); responses to antigens of Chlamydia trachomatis in subjects with severe trachomatous scarring. Clin. Exp. Immunol.105:429-435.
    OpenUrlCrossRefPubMedWeb of Science
  17. 17.↵
    Holland, M. J., R. L. Bailey, L. J. Hayes, H. C. Whittle, and D. C. Mabey. 1993. Conjunctival scarring in trachoma is associated with depressed cell-mediated immune responses to chlamydial antigens. J. Infect. Dis.168:1528-1531.
    OpenUrlCrossRefPubMedWeb of Science
  18. 18.↵
    Holland, M. J., D. J. Conway, T. J. Blanchard, O. M. Mahdi, R. L. Bailey, H. C. Whittle, and D. C. Mabey. 1997. Synthetic peptides based on Chlamydia trachomatis antigens identify cytotoxic T lymphocyte responses in subjects from a trachoma-endemic population. Clin. Exp. Immunol.107:44-49.
    OpenUrlCrossRefPubMed
  19. 19.↵
    Ito, J. I., and J. M. Lyons. 1999. Role of gamma interferon in controlling murine chlamydial genital tract infection. Infect. Immun.67:5518-5521.
    OpenUrlAbstract/FREE Full Text
  20. 20.↵
    Kolb, M., P. J. Margetts, D. C. Anthony, F. Pitossi, and J. Gauldie. 2001. Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. J. Clin. Investig.107:1529-1536.
    OpenUrlCrossRefPubMedWeb of Science
  21. 21.↵
    Mabey, D. C., R. L. Bailey, and Y. J. Hutin. 1992. The epidemiology and pathogenesis of trachoma. Rev. Med. Microbiol.3:112-119.
    OpenUrl
  22. 22.↵
    Mathews, S. A., K. M. Volp, and P. Timms. 1999. Development of a quantitative gene expression assay for Chlamydia trachomatis identified temporal expression of sigma factors. FEBS Lett.458:354-358.
    OpenUrlCrossRefPubMedWeb of Science
  23. 23.↵
    Meller, D., D. Q. Li, and S. C. Tseng. 2000. Regulation of collagenase, stromelysin, and gelatinase B in human conjunctival and conjunctivochalasis fibroblasts by interleukin-1beta and tumor necrosis factor-alpha. Investig. Ophthalmol. Vis. Sci.41:2922-2929.
    OpenUrlAbstract/FREE Full Text
  24. 24.↵
    Morrison, S. G., and R. P. Morrison. 2000. In situ analysis of the evolution of the primary immune response in murine Chlamydia trachomatis genital tract infection. Infect. Immun.68:2870-2879.
    OpenUrlAbstract/FREE Full Text
  25. 25.↵
    Morrison, S. G., H. Su, H. D. Caldwell, and R. P. Morrison. 2000. Immunity to murine Chlamydia trachomatis genital tract reinfection involves B cells and CD4+ T cells but not CD8+ T cells. Infect. Immun.68:6979-6987.
    OpenUrlAbstract/FREE Full Text
  26. 26.↵
    Mozzato-Chamay, N., O. S. Mahdi, O. Jallow, D. C. Mabey, R. L. Bailey, and D. J. Conway. 2000. Polymorphisms in candidate genes and risk of scarring trachoma in a Chlamydia trachomatis-endemic population. J. Infect. Dis.182:1545-1548.
    OpenUrlCrossRefPubMedWeb of Science
  27. 27.↵
    Opal, S. M., and V. A. DePalo. 2000. Anti-inflammatory cytokines. Chest117:1162-1172.
    OpenUrlCrossRefPubMedWeb of Science
  28. 28.↵
    Pasquale, L. R., M. E. Dorman-Pease, G. A. Lutty, H. A. Quigley, and H. D. Jampel. 1993. Immunolocalization of TGF-beta 1, TGF-beta 2, and TGF-beta 3 in the anterior segment of the human eye. Investig. Ophthalmol. Vis. Sci.34:23-30.
    OpenUrlAbstract/FREE Full Text
  29. 29.↵
    Perry, L. L., K. Feilzer, and H. D. Caldwell. 1997. Immunity to Chlamydia trachomatis is mediated by T helper 1 cells through IFN-gamma-dependent and -independent pathways. J. Immunol.158:3344-3352.
    OpenUrlAbstract
  30. 30.↵
    Perry, L. L., K. Feilzer, S. Hughes, and H. D. Caldwell. 1999. Clearance of Chlamydia trachomatis from the murine genital mucosa does not require perforin-mediated cytolysis or Fas-mediated apoptosis. Infect. Immun.67:1379-1385.
    OpenUrlAbstract/FREE Full Text
  31. 31.↵
    Ramsey, K. H., I. M. Sigar, L. S. Izzo, K. Cohoon, N. Shaba, and A. A. Izzo. 2002. Expression of matrix metalloproteases subsequent to Chlamydia trachomatis (mouse pneumonitis agent) genital tract infection in susceptible and resistant strains of female mice, p. 249-252. In J. S. Schachter (ed.), Chlamydial infections. Proceedings of the Tenth International Symposium on Human Chlamydial Infections. International Chlamydia Symposium, San Francisco, Calif.
  32. 32.↵
    Rank, R. G., K. H. Ramsey, E. A. Pack, and D. M. Williams. 1992. Effect of gamma interferon on resolution of murine chlamydial genital infection. Infect. Immun.60:4427-4429.
    OpenUrlAbstract/FREE Full Text
  33. 33.↵
    Rodel, J., E. Straube, W. Lungershausen, M. Hartmann, and A. Groh. 1998. Secretion of cytokines by human synoviocytes during in vitro infection with Chlamydia trachomatis. J. Rheumatol.25:2161-2168.
    OpenUrlPubMedWeb of Science
  34. 34.↵
    Rottenberg, M. E., A. Gigliotti-Rothfuchs, and H. Wigzell. 2002. The role of IFN-gamma in the outcome of chlamydial infection. Curr. Opin. Immunol.14:444-451.
    OpenUrlCrossRefPubMedWeb of Science
  35. 35.↵
    Sakaguchi, S. 2003. Regulatory T cells: mediating compromises between host and parasite. Nat. Immunol.4:10-11.
    OpenUrlCrossRefPubMedWeb of Science
  36. 36.↵
    Saren, P., H. G. Welgus, and P. T. Kovanen. 1996. TNF-alpha and IL-1beta selectively induce expression of 92-kDa gelatinase by human macrophages. J. Immunol.157:4159-4165.
    OpenUrlAbstract
  37. 37.↵
    Schonbeck, U., F. Mach, and P. Libby. 1998. Generation of biologically active IL-1 beta by matrix metalloproteinases: a novel caspase-1-independent pathway of IL-1 beta processing. J. Immunol.161:3340-3346.
    OpenUrlAbstract/FREE Full Text
  38. 38.↵
    Siwik, D. A., D. L. Chang, and W. S. Colucci. 2000. Interleukin-1beta and tumor necrosis factor-alpha decrease collagen synthesis and increase matrix metalloproteinase activity in cardiac fibroblasts in vitro. Circ. Res.86:1259-1265.
    OpenUrlAbstract/FREE Full Text
  39. 39.↵
    Thylefors, B., A. D. Negrel, R. Pararajasegaram, and K. Y. Dadzie. 1995. Global data on blindness. Bull. W. H. O.73:115-121.
    OpenUrlPubMedWeb of Science
  40. 40.↵
    West, S. K., B. Munoz, H. Mkocha, Y. H. Hsieh, and M. C. Lynch. 2001. Progression of active trachoma to scarring in a cohort of Tanzanian children. Ophthalmic Epidemiol.8:137-144.
    OpenUrlCrossRefPubMed
  41. 41.↵
    Wick, W., M. Platten, and M. Weller. 2001. Glioma cell invasion: regulation of metalloproteinase activity by TGF-beta. J. Neurooncol.53:177-185.
    OpenUrlCrossRefPubMed
  42. 42.↵
    Williams, D. M., B. G. Grubbs, E. Pack, K. Kelly, and R. G. Rank. 1997. Humoral and cellular immunity in secondary infection due to murine Chlamydia trachomatis. Infect. Immun.65:2876-2882.
    OpenUrlAbstract/FREE Full Text
  43. 43.↵
    Williams, D. M., B. G. Grubbs, S. Park-Snyder, R. G. Rank, and L. F. Bonewald. 1996. Activation of latent transforming growth factor beta during Chlamydia trachomatis-induced murine pneumonia. Res. Microbiol.147:251-262.
    OpenUrlCrossRefPubMed
  44. 44.↵
    Wong, T. T., A. L. Mead, and P. T. Khaw. 2003. Matrix metalloproteinase inhibition modulates postoperative scarring after experimental glaucoma filtration surgery. Investig. Ophthalmol. Vis. Sci.44:1097-1103.
    OpenUrlAbstract/FREE Full Text
  45. 45.↵
    Wong, T. T., C. Sethi, J. T. Daniels, G. A. Limb, G. Murphy, and P. T. Khaw. 2002. Matrix metalloproteinases in disease and repair processes in the anterior segment. Surv. Ophthalmol.47:239-256.
    OpenUrlCrossRefPubMedWeb of Science
  46. 46.↵
    Xue, M. L., D. Wakefield, M. D. Willcox, A. R. Lloyd, N. Di Girolamo, N. Cole, and A. Thakur. 2003. Regulation of MMPs and TIMPs by IL-1beta during corneal ulceration and infection. Investig. Ophthalmol. Vis. Sci.44:2020-2025.
    OpenUrlAbstract/FREE Full Text
  47. 47.↵
    Yang, X., J. Gartner, L. Zhu, S. Wang, and R. C. Brunham. 1999. IL-10 gene knockout mice show enhanced Th1-like protective immunity and absent granuloma formation following Chlamydia trachomatis lung infection. J. Immunol.162:1010-1017.
    OpenUrlAbstract/FREE Full Text
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Cytokine and Fibrogenic Gene Expression in the Conjunctivas of Subjects from a Gambian Community Where Trachoma Is Endemic
Matthew J. Burton, Robin L. Bailey, David Jeffries, David C. W. Mabey, Martin J. Holland
Infection and Immunity Nov 2004, 72 (12) 7352-7356; DOI: 10.1128/IAI.72.12.7352-7356.2004

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Cytokine and Fibrogenic Gene Expression in the Conjunctivas of Subjects from a Gambian Community Where Trachoma Is Endemic
Matthew J. Burton, Robin L. Bailey, David Jeffries, David C. W. Mabey, Martin J. Holland
Infection and Immunity Nov 2004, 72 (12) 7352-7356; DOI: 10.1128/IAI.72.12.7352-7356.2004
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KEYWORDS

conjunctiva
cytokines
Matrix Metalloproteinase 9
Trachoma

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