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Background:Recent reports have suggested an involvement of neutrophilic inflammation driven by interleukin (IL)-17 from Th17 cells, especially in severe, refractory asthma. It remains unknown about the possible interactions of this cytokine and other proinflammatory cytokines to direct neutrophilic airway inflammation.Materials and Methods:We evaluated the effects of IL-17A, IL-17E, and IL-17F in combination with other stimuli such as tumor necrosis factor (TNF) –α on the production and expression of IL-8 in human bronchial epithelial cells. We also studied their effects on other cytokine production. The possible role of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways was evaluated by specific inhibitors. We examined the effects of anti-asthma drugs, such as steroids or salmeterol.Results:IL-17A alone induced only a minimal effect on IL-8 expression. IL-17A, but not IL-17E or IL-17F, in combination with TNF-α showed a synergistic effect on IL-8 expression. Similar findings were found when combination with IL-1β and IL-17A were used, but such was not the case with lipopolysaccharide (LPS). In addition, we further found such synergy on GM-CSF production. The synergy with TNF-α and IL-17A was significantly inhibited by MAPKs inhibitors. Corticosteroids such as fluticasone propionate and dexamethasone, but not salmeterol, partially suppressed the IL-17A and TNF-α-induced IL-8 production.Conclusions:IL-17A in the combination with TNF-α or IL-1β showed a synergistic augmenting effect on IL-8 and GM-CSF production in human airway epithelial cells. [ABSTRACT FROM PUBLISHER]

Aim of the Study: Interleukin (IL)-10 is an anti-inflammatory cytokine, but its role in cigarette smoke (CS)-induced inflammation and chronic obstructive pulmonary disease (COPD) has not been fully elucidated. The purpose of this study was to investigate the effect of IL-10 deficiency on CS-induced pulmonary inflammation in mice in vivo and in vitro.Materials and Methods: IL-10-deficient and wild-type control mice with a C57BL6/J genetic background were exposed to CS, and inflammatory cells in bronchoalveolar lavage fluid (BALF) and mRNA of cytokines in lung were evaluated with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR).Results: During 12 days of daily CS exposure to wild-type mice, neutrophil counts in BAL fluid and tumor necrosis factor (TNF)-α mRNA expression were increased, peaked at day 8, and then declined on day 12 when the level of IL-10 reached its peak. In IL-10-deficient mice, neutrophil recruitment and TNF-α mRNA levels induced by CS exposure were significantly greater than those in wild-type mice. Keratinocyte-derived chemokine (KC; murine ortholog of human CXCL8) and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA levels or matrix metalloproteinase(MMP)-9 protein levels were not correlated with neutrophil count.Conclusions: IL-10 had a modulatory effect on CS-induced pulmonary neutrophilic inflammation and TNF-α expression in mice in vivo and therefore appears to be an important endogenous suppressor of airway neutrophilic inflammation. [ABSTRACT FROM PUBLISHER]

The authors used BALB/c and C57BL/6 mouse strains to search for genetically based differences in response to prolonged (6 months) low-dose (100 μg/m3) diesel exhaust particle (DEP) exposure from birth in terms of airway inflammatory responses. Histopathological assessment showed that inflammatory cells infiltrated the perivascular areas only in C57BL/6 mice. The count of DEP-laden alveolar macrophages in bronchoalveolar lavage (BAL) fluid was significantly greater in BALB/c mice (P < .05) than in C57BL/6 mice. The lymphocyte and eosinophil count in BAL fluid was significantly greater in C57BL/6 mice (P < .05) than in BALB/c mice. Immunoglobulin (Ig) IgG1 and IgG2 levels in serum, and the monocyte chemoattractant protein (MCP)-1 level in BAL fluid were significantly greater in BALB/c mice than in C57BL/6 mice. The interleukin (IL)-12 level in BAL fluid was significantly greater in C57BL/6 mice than in BALB/c mice, but the IL-13 level in BAL fluid was significantly less in BALB/c mice than in C57BL/6 mice. Glutathione S-transferase (GST) mRNA expression and protein production in lung tissues were significantly lower in C57BL/6 mice than in BALB/c mice, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in the lung tissues were significantly greater in C57BL/6 mice than in BALB/c mice. In conclusion, prolonged low-dose DEP exposure induces airway inflammatory responses that differ remarkably among mouse strains; these differences are caused by differences in the host defense response to the oxidative stress induced by DEP exposure and may be useful in the development of biomarkers. [ABSTRACT FROM AUTHOR]

Low-dose diesel exhaust particle (DEP) exposure induces airway inflammation and exaggerates asthmatic responses in mice, but it is unclear whether strains differ in their susceptibility to adverse effects from low-dose DEP exposure. The authors used BALB/c and C57BL/6 mouse strains to search for genetically based differences in response to low-dose DEP (100 µg/m3) exposure in terms of airway inflammatory response. The macrophage count in bronchoalveolar lavage (BAL) fluid soon after DE exposure began was significantly greater in C57BL/6 mice (P < .05) than that in BALB/c mice. The count did not increase significantly in BALB/c mice until later. Heme oxygenase-1 (HO-1) mRNA expression and protein production in lung tissues soon after exposure began were more marked in BALB/c mice than in C57BL/6 mice, but the reverse was true later on. The increases in interleukin (IL)-1β and interferon (IFN)-γ levels in BAL fluid after DE exposure were significant only in BALB/c mice; there were significantly increases in monocyte chemoattractant protein (MCP)-1, IL-12, IL-10, IL-4, and IL-13 in both strains, but these were more marked in C57BL/6 mice. These interstrain differences in airway inflammatory response after DE exposure were significantly attenuated by antioxidant N-acetylcysteine (NAC) treatment. Changes in airway hyperresponsiveness were independent of the airway inflammation induced by low-dose DEP. Thus, in BALB/c mice, innate immunity may play a central role in DE exposure response, whereas in C57BL/6 mice Th2-dominant responses play a central role. Low-dose DEP exposure induces airway inflammatory responses that differ among strains, and these differences may be caused by differences in sensitivity to oxidative stress. [ABSTRACT FROM AUTHOR]