Production of eosinophilic chemokines by normal pleural mesothelial cells.
Eosinophilic pleural effusion occurs in many diseases. The mechanisms of eosinophil accumulation are not well understood. We showed previously that eotaxin was readily detectable in most pleural effusions, and its concentration significantly correlated with eosinophil number. To test the hypothesis that pleural eotaxin is produced by resident mesothelial cells, we examined its production by normal pleural mesothelial cells (NPMC). Eotaxin was induced by tumor necrosis factor (TNF)-alpha or interleukin (IL)-4 and was drastically increased by their combination. In contrast, interferon (IFN)-gamma inhibited eotaxin production. Regulated on activation, normal T cells expressed and secreted (RANTES) was also induced by TNF-alpha and was drastically increased by the addition of IFN-gamma. These effects were observed at both protein and mRNA levels. Stabilization of RANTES mRNA was observed with IFN-gamma but not IL-4; neither cytokine stabilized eotaxin mRNA. Eosinophil chemoattractant activity in culture supernatants of NPMC stimulated with TNF-alpha plus IL-4 was diminished by an anti-eotaxin antibody; that induced by TNF-alpha plus IFN-gamma was attenuated by an anti-RANTES antibody. Thus, NPMC can produce eotaxin, and different cytokines act on NPMC to induce different chemokines by different mechanisms. IFN-gamma, a Th1 cytokine, acts at least at the posttranscriptional level to induce RANTES production, but it inhibits eotaxin production. In contrast, IL-4, a Th2 cytokine, acts at the transcriptional level to induce eotaxin.
Katayama
Hitoshi
H
Second Department of Internal Medicine, Ehime University School of Medicine, Onsen-gun, Ehime, Japan.
Yokoyama
Akihito
A
Kohno
Nobuoki
N
Sakai
Kimiko
K
Hiwada
Kunio
K
Yamada
Hirokazu
H
Hirai
Koichi
K
D002478:Cells, Cultured; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D019742:Chemokines, CC / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D004804:Eosinophils / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D010994:Pleura / Q000166:cytology* / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger
C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D017077:Culture Media, Conditioned; D016207:Cytokines; D012333:RNA, Messenger