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Infect. Immun. doi:10.1128/IAI.01313-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Intracellular interleukin-1{alpha} mediates interleukin-8 production induced by Chlamydia trachomatis infection via a mechanism independent of type I interleukin-1 receptor

Wen Cheng, Pooja Shivshankar, Youmin Zhong, Ding Chen, Zhongyu Li, and Guangming Zhong*

Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA; Departments of Immunology and Parasitology, The Central South University, Xiangya Medical School, 168 Tongzipo Rd., Changsha, Hunan 410013, The People's Republic of China

* To whom correspondence should be addressed. Email: Zhongg{at}UTHSCSA.EDU.


   Abstract

Chlamydia trachomatis infection induces a wide array of inflammatory cytokines and chemokines, which may contribute to Chlamydia-induced pathologies. However, the precise mechanisms on how Chlamydia induces cytokines remain unclear. Here, we have demonstrated that the proinflammatory cytokine interleukin (IL)-1{alpha} plays an essential role in chlamydial induction of the chemokine IL-8. Cells deficient in IL-1{alpha} expression or IL-1{alpha}-competent cells treated with IL-1{alpha}-specific SiRNA failed to produce IL-8 in response to chlamydial infection. However, neutralization of extracellular IL-1{alpha} or blockade of or deficiency in type I IL-1 receptor (IL-1RI) signaling did not affect chlamydial induction of IL-8 in cells capable of producing IL-1{alpha}. These results suggest that IL-1{alpha} can mediate the chlamydial induction of IL-8 via an intracellular mechanism independent of IL-1RI especially during the early stage of infection cycle. This conclusion is further supported by the observations that expression of a transgene-encoded full-length IL-1{alpha} fusion protein in the nuclei enhanced IL-8 production and nuclear localization of Chlamydia-induced precursor IL-1{alpha} correlated with chlamydial induction of IL-8. Thus, we have identified a novel mechanism for chlamydial induction of the chemokine IL-8.




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