Interleukin-27 induces a STAT1/3- and NF-kappaB-dependent proinflammatory cytokine profile in human monocytes.
IL-27 is a heterodimeric cytokine bridging innate and adaptive immunity by playing a role in the activation of naive T cells and in development of Th1 cells. Additionally, recent evidence supports a role for IL-27 in the activation of monocytic cells. Both pro-inflammatory and anti-inflammatory activities have been attributed to IL-27; however, the role played by IL-27 in the activation of human monocytic cells in terms of cytokine production has not been well described. Our results show that IL-27 is a strong inducer of proinflammatory cytokine and chemokine expression, including enhancement of IL-6, IP-10, MIP-1alpha, MIP-1beta, and TNF-alpha expression in human primary monocytes. Furthermore, we observed that IL-27-induced cytokine and chemokine production was mediated by STAT1, STAT3, and NF-kappaB activation. Understanding how IL-27 exerts its effects on monocytic cells will identify important molecular mechanisms in the regulation of immune responses, particularly in the modulation of monocyte activation.
Department of Microbiology and Immunology, Queen's University, Kingston, Ontario K7L 3N6, Canada.
Christina
C
Guzzo
Nor Fazila
NF
Che Mat
Katrina
K
Gee
D002460:Cell Line; D002478:Cells, Cultured / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D007249:Inflammation; D020381:Interleukin-17 / Q000378:metabolism*; D053613:Janus Kinase 1 / Q000378:metabolism; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
D016207:Cytokines; D020381:Interleukin-17; D016328:NF-kappa B; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053613:Janus Kinase 1