The synergistic induction of CXCL1 by IL-17 and TNF-α in ATII cells is mediated by NADPH oxidase. A: Normoxic (Norm) ATII cells treated with TNF-α (TNF, 50 ng/ml) or IL-17 (50 ng/ml) significantly increased CXCL1 production compared with Norm alone. Apocynin (Apo, 600 μM) treatment significantly attenuated TNF-α-induced, but not IL-17-induced, CXCL1 production. Combined treatment with IL-17 and TNF-α synergistically activated ATII cells to produce a multifold increase in CXCL1 production compared with either treatment alone, which is significantly attenuated by apocynin. The small graph in the inset depicts an enlargement of the first three data values of the larger graph to better view their relationship. *P < 0.05 vs. Norm; #P < 0.05 Norm+TNF; ##P < 0.05 vs. Norm+IL-17+TNF; ND = not detected; n = 8/group. B: HR-exposed ATII cells significantly increased CXCL1 production compared with normoxia, which was significantly attenuated by apocynin pretreatment. Treatment with TNF-α but not IL-17, significantly enhanced CXCL1 production by ATII cells compared with HR alone, which was significantly attenuated by apocynin. Combined treatment of HR-exposed ATII cells with IL-17 and TNF-α synergistically increased CXCL1 production compared with treatment with HR+TNF, which was significantly attenuated by apocynin pretreatment. *P < 0.05 vs. Norm; #P < 0.05 vs. HR; ##P < 0.05 vs. HR+IL-17; §P < 0.05 vs. HR+TNF; §§P < 0.05 vs. HR+IL-17+TNF; n = 8/group. C: HR significantly increased CXCL1 production by primary WT ATII cells compared with normoxia, which was significantly attenuated in HR-exposed primary ATII cells from p47phox−/− mice. *P < 0.05 vs. WT Norm; #P < 0.05 WT HR.