Regulation of uteroglobin/Clara cell protein expression after acute lung exposure to an organophosphoreted insecticide.
Uteroglobin (UG) or Clara cell protein (CC16), the main secretory product of bronchiolar Clara cells, plays an important protective role in the respiratory tract against inflammatory processes. In the lung, protein secretion is regulated by glucocorticoids, but also proinflammatory cytokines, such as interferon-gamma (IFN-gamma) and TNF-alpha, have been found to modulate the expression of this peptide. We have previously demonstrated that the acute exposure to an organophosphoreted insecticide induces an enhanced production of UG/CC16 by Clara cells. In the present report, we worked with intact and adrenalectomised (ADX) animals to study the mechanism involved in the UG/CC16 increase caused by the insecticide and the role played by a glucocorticoid (dexamethasone; DEX). In intact rats we found that DEX treatment could not reproduce such an increase of UG/CC16 synthesis with pharmacological doses. In ADX rats, even though glucocorticoid deprivation provoked a strong inhibition of UG/CC16 synthesis, the exposure to the organophosphoreted insecticide stimulated the synthesis of the protein, shown by the great accumulation of secretory granules in the cytoplasm of Clara cells and the increase of UG/CC16 detected by immunocytochemistry and western blot. These results imply that glucocorticoids are not essential to trigger the increase of UG/CC16 in response to an injury, and they also suggest an involvement of other molecules associated with inflammation. In coincidence with these observations, we have found that IFN-gamma, a proinflammatory cytokine, increased after insecticide exposition in both groups, intact and ADX, mainly in ADX rats. The stimulation of UG/CC16 synthesis occurring during inflammatory processes of the respiratory tract caused by acute inhalation of a toxicant appears to be functional without the intervention of glucocorticoids and mediated by IFN-gamma as a mechanism for local control of the inflammatory response.
Elia
Jorge
J
Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Aoki
Agustín
A
Maldonado
Cristina A
CA
D000315:Adrenalectomy; D000818:Animals; D015153:Blotting, Western; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D007150:Immunohistochemistry; D007306:Insecticides / Q000633:toxicity*; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D016253:Microscopy, Immunoelectron; D009943:Organophosphorus Compounds; D011506:Proteins / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014598:Uteroglobin / Q000276:immunology / Q000378:metabolism*
D005938:Glucocorticoids; D007306:Insecticides; D009943:Organophosphorus Compounds; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma; D014598:Uteroglobin