Clara cell 10-KDA protein inhibits endotoxin-induced airway contraction in isolated perfused rat lungs.
Clara cell 10-kDa protein (CC10) is a major component of bronchoalveolar lavage fluid and is suggested to be a natural regulator of airway inflammation, possibly through its effects on the proinflammatory enzyme(s), phospholipase A2. We examined the effect of recombinant human (rh) CC10 on endotoxin-induced airway contraction and cytokine release in isolated perfused rat lungs. We found that rhCC10 added to the lung perfusate abolished the endotoxin-induced airway contraction, and that it inhibited both the release of interleukin-1 beta and interleukin-6 into the lung perfusate and the release of tumor necrosis factor-alpha into the pulmonary lavage fluid. By contrast, the levels of interferon-gamma were unaffected by CC10 administration. Rutin, a phospholipase A2 inhibitor, and N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, also attenuated the contraction induced by endotoxin. These findings demonstrate that rhCC10 inhibits endotoxin-induced airway contraction and the release of proinflammatory cytokines (interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha) in isolated perfused rat lungs. The results also indicate that phospholipase A2 and nitric oxide are involved in the airway contraction in this model, possibly through their influence on the production of eicosanoids.
Nosratabadi
Ali Reza
AR
Department of Molecular and Clinical Medicine, Division of Occupational and Environmental Medicine, Faculty of Health Sciences, University of Linköping, S-581 85 Linköping, Sweden. reza.nosratabadi@lio.se
Ljungman
Anders G
AG
Lindahl
Mats
M
Welch
Richard
R
Pilon
Aprile
A
Tagesson
Christer
C
D000109:Acetylcholine / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012431:Rutin / Q000494:pharmacology; D014598:Uteroglobin / Q000494:pharmacology*
D016207:Cytokines; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; C556389:SCGB1A1 protein, human; C556391:Scgb1a1 protein, rat; D012431:Rutin; D014598:Uteroglobin; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester