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Am J Physiol Lung Cell Mol Physiol 287: L1186-L1192, 2004. First published August 20, 2004; doi:10.1152/ajplung.00170.2004
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Early response to bleomycin is characterized by different cytokine and cytokine receptor profiles in lungs

Eleonora Cavarra,1 Fabio Carraro,2 Silvia Fineschi,1 Antonella Naldini,2 Barbara Bartalesi,1 Annalisa Pucci,2 and Giuseppe Lungarella1

Departments of 1Physiopathology, Experimental Medicine & Public Health and 2Physiology, University of Siena, Siena, Italy I-53100

Submitted 12 May 2004 ; accepted in final form 18 August 2004

The sensitivity to the fibrosis-inducing effect of bleomycin varies considerably from species to species, the reasons for which are unknown. The variability of the response in different strains of mice is well documented. Recent evidence indicates that the upregulated expression of cytokines and cytokine receptors may be involved. We evaluated the expression pattern of some cytokines and their receptors in C57Bl/6J bleomycin-sensitive and Balb/C bleomycin-resistant mice. Animals from both strains received, under ether anesthesia, either saline (50 µl) or bleomycin (0.1 U/50 µl) intratracheally. At various times after the treatment, the lungs were analyzed for cytokines and cytokine receptors by histochemistry and their mRNA by RNase protection assay. A significantly increased expression of TNF-{alpha} and IL-1{beta} was observed in both strains. However, an upregulated lung expression for TNF-{alpha} and IL-1 receptors was observed in C57Bl/6J-sensitive animals only. This profile is evident from 63 h onward. In addition to TNF-{alpha}, bleomycin administration also resulted in the upregulated expression of TGF-{beta} in the lungs of both strains at 8 h and in an enhanced expression of TGF-{beta} receptors I and II in C57Bl/6J mice only. The upregulation of TGF-{beta} receptor expression was preceded in this strain by an increased expression of IL-4, IL-13, and IL-13 receptor-{alpha} (at 8 h after bleomycin) and followed by an upregulation of gp130 and IL-6. The difference we observed in the cytokine receptor profile may offer an additional explanation for the different fibrogenic response of the two mouse strains to bleomycin.

mouse strains; early fibrogenic response; cytokine and receptor profile


Address for reprint requests and other correspondence: G. Lungarella, Dept. of Physiopathology, Experimental Medicine & Public Health, Univ. of Siena, Via Aldo Moro, Siena, Italy I-53100 (E-mail: lungarella{at}unisi.it)




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