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 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.
Han
S J
SJ
Department of Biochemistry and Molecular Biology, Hanyang University, Kyunggi-do, Seoul, Korea.
Kim
J H
JH
Noh
Y J
YJ
Chang
H S
HS
Kim
C S
CS
Kim
K S
KS
Ki
S Y
SY
Park
C S
CS
Chung
I Y
IY
D054413:Chemokine CCL11; D019742:Chemokines, CC; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004804:Eosinophils / Q000378:metabolism*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000378:metabolism; D017403:In Situ Hybridization; D015848:Interleukin-5 / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002630:Chemotactic Factors; D016207:Cytokines; D015848:Interleukin-5; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha