Intracellular interleukin-1alpha mediates interleukin-8 production induced by Chlamydia trachomatis infection via a mechanism independent of type I interleukin-1 receptor.
Chlamydia trachomatis infection induces a wide array of inflammatory cytokines and chemokines, which may contribute to chlamydia-induced pathologies. However, the precise mechanisms by which Chlamydia induces cytokines remain unclear. Here we demonstrate that the proinflammatory cytokine interleukin-1alpha (IL-1alpha) plays an essential role in chlamydial induction of the chemokine IL-8. Cells deficient in IL-1alpha expression or IL-1alpha-competent cells treated with IL-1alpha-specific small interfering RNA failed to produce IL-8 in response to chlamydial infection. However, neutralization of extracellular IL-1alpha 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-1alpha. These results suggest that IL-1alpha can mediate the chlamydial induction of IL-8 via an intracellular mechanism independent of IL-1RI, especially during the early stage of the infection cycle. This conclusion is further supported by the observations that expression of a transgene-encoded full-length IL-1alpha fusion protein in the nuclei enhanced IL-8 production and that nuclear localization of chlamydia-induced precursor IL-1alpha correlated with chlamydial induction of IL-8. Thus, we have identified a novel mechanism for chlamydial induction of the chemokine IL-8.
Cheng
Wen
W
Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Shivshankar
Pooja
P
Zhong
Youmin
Y
Chen
Ding
D
Li
Zhongyu
Z
Zhong
Guangming
G
D000818:Animals; D002460:Cell Line; D002692:Chlamydia trachomatis / Q000276:immunology*; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006801:Humans; D053582:Interleukin-1alpha / Q000172:deficiency / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008856:Microscopy, Fluorescence; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053582:Interleukin-1alpha; D016209:Interleukin-8; D017472:Receptors, Interleukin-1