Interleukin (IL)-5 Downregulates Tumor Necrosis Factor (TNF)–Induced Eotaxin Messenger RNA (mRNA) Expression in Eosinophils

Abstract

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 interesting to know whether eosinophils are able to produce their own eotaxin and participate in recruitment of themselves in response to inflammation. To this 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 was, 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 major factor of eosinophil survival in vivo and in vitro, was also able to induce a modest level of eotaxin mRNA but inhibited TNF-induced eotaxin mRNA expression in a dose-response manner. Dexamethasone inhibited TNF-induced eotaxin mRNA expression. This result was consistent with that from reverse transcription/polymerase chain reaction followed by Southern blot analysis. Unlike the little expression of eotaxin mRNA in the absence of stimuli, the measurement of eotaxin protein revealed that a considerable amount of eotaxin protein was constitutively produced in unstimulated eosinophils. Its expression was upregulated by TNF and IL-5 as well. However, the inhibitory effect of IL-5 on TNF-mediated eotaxin protein production was not as pronounced as that on eotaxin mRNA induction. Collectively, these data reflect the complex physiology of eosinophils in the expression of eotaxin gene upon the exposure to their survival and/or death factors.

A Single Nucleotide Polymorphism on the Promoter of eotaxin1 Associates with Its mRNA Expression and Asthma Phenotypes

“…To confirm that the EOTϪ384AϾG allele is a determinant for eotaxin1 gene transcription, the mRNA expression levels in PBMC carrying polymorphic alleles at the EOTϪ384AϾG loci were compared after stimulation with TNF-␣ which has been known to potent stimulator for eotaxin mRNA and protein production from eosinophils (38) as well as epithelial cells (26,39). Asthmatics having the homozygotic wild alleles (Ϫ384AϾG AA) showed significantly higher mRNA expression after stimulation with TNF-␣ than those having the minor allele homozygote (Ϫ384AϾG GG) (Fig.…”

Association of Interleukin-5 and Eotaxin with Acute Exacerbation of Asthma

“…2) suggests the possibility that IL-5 and eotaxin are produced by the same cells or that they mutually stimulate their production. However, eotaxin is expressed constitutively in epithelial and endothelial cells, and on macrophages, T cells and eosinophils upon activation [16, 31], whereas IL-5 is synthesized primarily by activated Th2 lymphocytes and mast cells [10]. Therefore, it is unlikely that the same cells produce IL-5 and eotaxin.…”

“…In our analysis of sputum from patients with acute exacerbation of asthma, the number of eosinophils was found to be 5 times more than that of macrophages. Furthermore, because IL-5 is able to stimulate eosinophils to synthesize eotaxin in vitro [31], eosinophil-derived eotaxin can provide an important autocrine pathway for the accumulation of eosinophils in cases of acute exacerbation. However, the rate of eotaxin expression on eosinophils was much lower than that on macrophages, regardless of the asthma type, in the present study (table 3) and other studies [17, 18, 21], which could decrease the possibility that eosinophils are the principal source of eotaxin.…”

Interferon-γ Inhibits in vitro Mobilization of Eosinophils by Interleukin-5

“…We found that TNF and IL-6, but not IL-1β, are the cytokines that induce significant eosinophil shape change. TNF prolongs eosinophil survival and induces eosinophil eotaxin production, and enhances eosinophil recruitment by induction of endothelial cell adhesiveness [21, 22, 23]. An increased level of TNF is also found in asthmatic airways [24].…”