Interleukin (IL)-5 downregulates tumor necrosis factor (TNF)-induced eotaxin messenger RNA (mRNA) expression in eosinophils - Induction of eotaxin mRNA by TNF and IL-5 in eosinophils

An eotaxin is a chemoattractant specific for eosinophils that are known to play a role in helminth infection and allergic responses. Although several cellular sources have been reported to produce eotaxin, it would be interes ting to know whether eosinophils are able to produce their own eotaxin and participate in recruitment of themselves in response to inflammation. To th is end, a cloned eotaxin complementary DNA was transcribed in vitro to use as a probe for detecting eotaxin messenger RNA (mRNA), and eotaxin protein levels were determined by enzyme-linked immunosorbent assay. Eotaxin mRNA w as, as analyzed by in situ hybridization, rarely detectable in unstimulated eosinophils, but was strongly induced in eosinophils when stimulated with tumor necrosis factor (TNF). Interleukin (IL)-5, which is known to be a maj or factor of eosinophil survival in vivo and in vitro, was also able to ind uce a modest level of eotaxin mRNA but inhibited TNF-induced eotaxin mRNA e xpression in a dose-response manner. Dexamethasone inhibited TNF-induced eo taxin mRNA expression. This result was consistent with that from reverse tr anscription/polymerase chain reaction followed by Southern blot analysis. U nlike the little expression of eotaxin mRNA in the absence of stimuli, the measurement of eotaxin protein revealed that a considerable amount of eotax in protein was constitutively produced in unstimulated eosinophils. Its exp ression was upregulated by TNF and IL-5 as well. However, the inhibitory ef fect of IL-5 on TNF-mediated eotaxin protein production was not as pronounc ed as that on eotaxin mRNA induction. Collectively, these data reflect the complex physiology of eosinophils in the expression of eotaxin gene upon th e exposure to their survival and/or death factors.