First Author | Ramadas RA | Year | 2012 |
Journal | PLoS One | Volume | 7 |
Issue | 9 | Pages | e45784 |
PubMed ID | 23029241 | Mgi Jnum | J:191979 |
Mgi Id | MGI:5463713 | Doi | 10.1371/journal.pone.0045784 |
Citation | Ramadas RA, et al. (2012) IL-36alpha exerts pro-inflammatory effects in the lungs of mice. PLoS One 7(9):e45784 |
abstractText | Interleukin (IL-) 36 cytokines (previously designated as novel IL-1 family member cytokines; IL-1F5- IL-1F10) constitute a novel cluster of cytokines structurally and functionally similar to members of the IL-1 cytokine cluster. The effects of IL-36 cytokines in inflammatory lung disorders remains poorly understood. The current study sought to investigate the effects of IL-36alpha (IL-1F6) and test the hypothesis that IL-36alpha acts as a pro-inflammatory cytokine in the lung in vivo. Intratracheal instillation of recombinant mouse IL-36alpha induced neutrophil influx in the lungs of wild-type C57BL/6 mice and IL-1alphabeta(-/-) mice in vivo. IL-36alpha induced neutrophil influx was also associated with increased mRNA expression of neutrophil-specific chemokines CXCL1 and CXCL2 in the lungs of C57BL/6 and IL-1alphabeta(-/-) mice in vivo. In addition, intratracheal instillation of IL-36alpha enhanced mRNA expression of its receptor IL-36R in the lungs of C57BL/6 as well as IL-1alphabeta(-/-) mice in vivo. Furthermore, in vitro incubation of CD11c(+) cells with IL-36alpha resulted in the generation of neutrophil-specific chemokines CXCL1, CXCL2 as well as TNFalpha. IL-36alpha increased the expression of the co-stimulatory molecule CD40 and enhanced the ability of CD11c(+) cells to induce CD4(+) T cell proliferation in vitro. Furthermore, stimulation with IL-36alpha activated NF-kappaB in a mouse macrophage cell line. These results demonstrate that IL-36alpha acts as a pro-inflammatory cytokine in the lung without the contribution of IL-1alpha and IL-1beta. The current study describes the pro-inflammatory effects of IL-36alpha in the lung, demonstrates the functional redundancy of IL-36alpha with other agonist cytokines in the IL-1 and IL-36 cytokine cluster, and suggests that therapeutic targeting of IL-36 cytokines could be beneficial in inflammatory lung diseases. |