Immunomodulatory effects of erythromycin and its derivatives on human T-lymphocyte in vitro.
To elucidate the immunomodulatory mechanisms of macrolides, we investigated here the effects of erythromycin (EM) and its derivatives, 1 and 2, which show no antibacterial activity, on the proliferation and the activation of the transcription factor nuclear factor-kappaB (NF-kappaB) in Jurkat T cells. MTT assay revealed that EM, 1 and 2 could inhibit T lymphocyte proliferation markedly. Flow cytometry and TUNEL analysis showed EM (30 microg/mL-100 microg/mL) and 1 (3 microg/mL-30 microg/mL) could induce T lymphocyte apoptosis, 2 (3 microg/mL-30 microg/mL) induced a cell cycle arrest in G(2)/M. RT-PCR and Western blotting analysis conformed that EM and its two derivatives could inhibit the expressions of NF-kappaB mRNA and protein. Taken together, these data suggest EM and its derivatives, 1 and 2, have immunomodulatory effect, presumably via an interaction with the NF-kappaB expression, inhibiting the proliferation of T lymphocyte, implicating an approach for the development of new drugs for treating inflammatory diseases.
Wu
Lan
L
Department of Geratology, The First Affiliated Hospital, Chinese Medical University, Shenyang, People's Republic of China. wulan_2000@sina.com
Zhang
Weige
W
Tian
Liang
L
Bao
Kai
K
Li
Pengfei
P
Lin
Jie
J
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D016328:NF-kappa B / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D013778:Tetrazolium Salts; D013844:Thiazoles
D000900:Anti-Bacterial Agents; D007155:Immunologic Factors; D016328:NF-kappa B; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; D004917:Erythromycin; C022616:thiazolyl blue