Peroxisome proliferator-activated receptors are expressed in human cultured mast cells: a possible role of these receptors in negative regulation of mast cell activation

We investigated the expression of peroxisome proliferator-activated recepto rs (PPAR) in human cultured mast cells (HCMC) by using the reverse transcri ption-polymerase chain reaction. HCMC expressed mRNA of PPAR beta, gamma1, and gamma2 constitutively, whereas PPAR alpha was not detected. Though PPAR gamma2 was expressed weakly, activation of HCMC with anti-IgE after IgE se nsitization or with calcium ionophore plus phorbol ester resulted in increa sed expression of PPAR gamma2 specifically. These stimuli did not influence the expression of PPAR alpha and beta. In addition, provocation of HCMC wi th IgE or with IL-4 increased the mRNA level of PPAR gamma2, and a synergis tic effect was observed with the combination of IgE plus IL-4. To investiga te a possible role of PPAR in mast cells, we examined the effects of PPAR a gonists on cytokine production by HCMC. Prostaglandin (PG) D-2, Delta (12)- PGJ(2), 15deoxy-Delta (12,14)-PGJ(2) (15d-PGJ(2)), and troglitazone, all of which are PPAR gamma agonists, attenuated the production of granulocyte-ma crophage colony-stimulating factor by anti-IgE-stimulated HCMC. A similar e ffect was observed with carbaprostacyclin, a PPAR beta agonist, but not wit h PPAR alpha agonists. Anti-IgE-induced expression of cytokine mRNA, such a s TNF-alpha, IL-5 and macrophage inflammatory protein-1 alpha mRNA, was als o reduced by the treatment with these PPAR gamma agonists. Though only Delt a (12)-PGJ(2) and 15d-PGJ(2) revealed an inhibitory effect on histamine rel ease, leukotriene C-4 release from HCMC was suppressed by all tested PPAR g amma agonists. These results indicate that HCMC express PPAR beta and gamma 1/2, which might negatively regulate the activation of HCMC.