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Am J Physiol Lung Cell Mol Physiol (August 20, 2004). doi:10.1152/ajplung.00170.2004
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Submitted on May 12, 2004
Accepted on August 18, 2004

EARLY RESPONSE TO BLEOMYCIN IS CHARACTERISED BY DIFFERENT CYTOKINE AND CYTOKINE RECEPTOR PROFILES IN THE LUNGS OF FIBROSIS-PRONE AND FIBROSIS-RESISTANT MICE

Eleonora Cavarra1, Fabio Carraro2, Silvia Fineschi1, Antonella Naldini2, Barbara Bartalesi1, Annalisa Pucci2, and Giuseppe Lungarella1*

1 Department of Physiopathology, Experimental Medicine & Public Health, University of Siena, Siena, Italy
2 Department of Physiology, University of Siena, Siena, Italy

* To whom correspondence should be addressed. E-mail: lungarella{at}unisi.it.

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 up-regulated 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 anaesthesia, either saline (50µl), or bleomycin (0.1U/50µl) intratracheally. At various times after the treatment, the lungs were analysed for cytokines and cytokine receptors by histochemistry and their mRNA by Ribonuclease Protected Assay. A significantly increased expression of TNF-alpha and IL-1 beta was observed in both strains. However, an up-regulated lung expression for TNF-alpha and IL-1 receptors, was observed in C57Bl/6J sensitive animals only. This profile is evident from 63 hours onward. In addition to TNF-alpha, bleomycin administration also resulted in the up-regulated expression of TGF-beta in the lungs of both strains at 8 hours, 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 hours after bleomycin) and followed by an up-regulation 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.




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