Immunomodulation by biphalin, dimeric synthetic opioid peptide, and its analog.
The opioid pentapeptides called enkephalins were originally described as the endogenous ligands for the opioid receptors. Although their precise physiological significance still remains elusive, the enkephalins have been reported to exhibit analgesic, antidepressant, antianxiety and anticonvulsant activities. In addition, enkephalins have also been shown to act as immunomodulator. The first generation of dimeric peptides was derived from enkephalins. Biphalin [(Tyr-D-Ala-Gly-Phe-NH)2] is a bivalent opioid analog containing two tyrosine residues. We have evaluated the immunomodulatory properties of biphalin and its analogs in various in vitro tests. We report that biphalin and one of its analogs [Tyr-D-Ala-Gly-Phe-NH.NH-Phe(p-Cl)-H] stimulate human T cell proliferation, natural killer (NK) cell cytotoxicity in vitro and interleukin-2 (IL-2) production. Biphalin and its analog also released chemokine like factor in the culture supernatant that was responsible for increased chemotaxis of monocytes. Furthermore, these peptides inhibited tumor necrosis factor (TNF-alpha) production in lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) and nitric oxide (NO) production in mouse macrophage cells, RAW 264.7. Our observations suggest immunomodulatory property of biphalin and its analog.
Mehrotra
S
S
Department of Immunology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Prajapati
R K
RK
Haq
W
W
Singh
V K
VK
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D004745:Enkephalins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000276:Adjuvants, Immunologic; D004745:Enkephalins; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C053673:biphalin