IL-17A synergistically stimulates TNF-α-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation.
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.



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.



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.



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.
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Kojiro
K
Honda
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Hiroo
H
Wada
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Masuo
M
Nakamura
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Keitaro
K
Nakamoto
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Toshiya
T
Inui
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Mitsuru
M
Sada
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Takashi
T
Koide
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Saori
S
Takata
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Takuma
T
Yokoyama
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Takeshi
T
Saraya
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Daisuke
D
Kurai
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Haruyuki
H
Ishii
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Hajime
H
Goto
a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
Hajime
H
Takizawa
D002478:Cells, Cultured; D004357:Drug Synergism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000209:etiology; D020381:Interleukin-17 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C508717:IL17A protein, human; D020381:Interleukin-17; D016209:Interleukin-8; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020928:Mitogen-Activated Protein Kinases
IL-17; asthma; corticosteroid; neutrophil