| First Author | Liu Y | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 5 | Pages | 3197-205 |
| PubMed ID | 21282514 | Mgi Jnum | J:169376 |
| Mgi Id | MGI:4940908 | Doi | 10.4049/jimmunol.1002016 |
| Citation | Liu Y, et al. (2011) IL-17A and TNF-{alpha} Exert Synergistic Effects on Expression of CXCL5 by Alveolar Type II Cells In Vivo and In Vitro. J Immunol 186(5):3197-205 |
| abstractText | CXCL5, a member of the CXC family of chemokines, contributes to neutrophil recruitment during lung inflammation, but its regulation is poorly understood. Because the T cell-derived cytokine IL-17A enhances host defense by triggering production of chemokines, particularly in combination with TNF-alpha, we hypothesized that IL-17A would enhance TNF-alpha-induced expression of CXCL5. Intratracheal coadministration of IL-17A and TNF-alpha in mice induced production of CXCL1, CXCL2, and CXCL5, which was associated with increased neutrophil influx in the lung at 8 and 24 h. The synergistic effects of TNF-alpha and IL17A were greatly attenuated in Cxcl5(-/-) mice at 24 h, but not 8 h, after exposure, a time when CXCL5 expression was at its peak in wild-type mice. Bone marrow chimeras produced using Cxcl5(-/-) donors and recipients demonstrated that lung-resident cells were the source of CXCL5. Using differentiated alveolar epithelial type II (ATII) cells derived from human fetal lung, we found that IL-17A enhanced TNF-alpha-induced CXCL5 transcription and stabilized TNF-alpha-induced CXCL5 transcripts. Whereas expression of CXCL5 required activation of NF-kappaB, IL-17A did not increase TNF-alpha-induced NF-kappaB activation. Apical costimulation of IL-17A and TNF-alpha provoked apical secretion of CXCL5 by human ATII cells in a transwell system, whereas basolateral costimulation led to both apical and basolateral secretion of CXCL5. The observation that human ATII cells secrete CXCL5 in a polarized fashion may represent a mechanism to recruit neutrophils in host defense in a fashion that discriminates the site of initial injury. |
