Acidic mammalian chitinase in asthmatic Th2 inflammation and IL-13 pathway activation.
Chitin is a surface component of parasites and insects, and chitinases are induced in lower life forms during infections with these agents. Although chitin itself does not exist in humans, chitinases are present in the human genome. We show here that acidic mammalian chitinase (AMCase) is induced via a T helper-2 (Th2)-specific, interleukin-13 (IL-13)-mediated pathway in epithelial cells and macrophages in an aeroallergen asthma model and expressed in exaggerated quantities in human asthma. AMCase neutralization ameliorated Th2 inflammation and airway hyperresponsiveness, in part by inhibiting IL-13 pathway activation and chemokine induction. AMCase may thus be an important mediator of IL-13-induced responses in Th2-dominated disorders such as asthma.
Zhu
Zhou
Z
Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, Department of Internal Medicine, 300 Cedar Street, TAC S-441, New Haven, CT 06520-8057, USA.
Zheng
Tao
T
Homer
Robert J
RJ
Kim
Yoon-Keun
YK
Chen
Ning Yuan
NY
Cohn
Lauren
L
Hamid
Qutayba
Q
Elias
Jack A
JA
D000328:Adult; D000485:Allergens; D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018925:Chemokines / Q000378:metabolism; D002686:Chitin / Q000378:metabolism; D002688:Chitinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007106:Immune Sera; D018793:Interleukin-13 / Q000378:metabolism*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000201:enzymology* / Q000276:immunology; D016676:Macrophages, Alveolar / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D020545:Respiratory Mucosa / Q000201:enzymology; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation
D000485:Allergens; D018925:Chemokines; D007106:Immune Sera; D018793:Interleukin-13; D007378:Interleukins; D002686:Chitin; D010047:Ovalbumin; C499255:AMCase, mouse; C499254:CHIA protein, human; D002688:Chitinases