Biomedical subjects

M M Dhar

Publications and source records attributed to M M Dhar.

At least 19 recordsLinked to original sources

PubMed2003

Inhibition of anti-CD3 and interleukin-2 stimulated T lymphocyte proliferation by peptidomimetic opioid compound.

In continuation to our earlier studies with peptidomimetic opioid compounds, we have further investigated immunosuppressive properties of one of our peptidomimetic compound (Tyr-NH-CH2-CH2-O-Phe-NH2) using peripheral blood mononuclear cells (PBMCs) of healthy volunteers. Peptidomimetic compound was evaluated for its effect on anti-CD3 and recombinant human interleukin-2 (rhIL-2) stimulated lymphocyte proliferation in vitro and lipopolysaccharide (LPS) induced activation of mitogen activated protein kinase (MAPK, pp42/44) in mouse macrophage cells (RAW 264.7). Our results show the immunosuppressive potential of synthetic peptidomimetic compound. This compound significantly inhibited anti-CD3 and rhIL-2 stimulated lymphocyte proliferation in vitro. However, this peptidomimetic compound did not show any effect on LPS induced MAPK activation. These observations suggest that above peptidomimetic compound has potential to inhibit immune responses mediated by lymphocytes.

Animals↗

PubMed2002

Inhibition of antigen specific lymphocyte proliferation and cytokine stimulation by peptidomimetic opioid compound.

In sequel to our preliminary observations with peptidomimetic opioid compounds, we have further investigated immunomodulatory activity of one peptidomimetic compound (Tyr-NH-CH2-CH2-O-Phe-NH2) with peripheral blood mononuclear cells (PBMCs) of healthy volunteers/tuberculosis patients. This peptidomimetic compound was evaluated for its effect on purified protein derivative (PPD) stimulated lymphocyte proliferation in vitro, production of Th1 and Th2 cytokines by ELISA and ribonuclease protection assay. Our study shows the immunosuppressive potential of above synthetic peptidomimetic compound. This compound inhibited PPD stimulated human lymphocyte proliferation and this inhibition was reversed by opioid receptor antagonist, naloxone. Its immunosuppressive effect was further demonstrated by inhibition of interleukin-9 (IL-9), IL-10 but failed to influence IL-2, IL-15 and interferon-y (IFN-gamma) in PPD stimulated human PBMCs.

Animals↗

PubMed2001

Immunomodulation by opioid peptidomimetic compound.

OBJECTIVE: As a follow-up to our earlier studies on immunomodulation with opioid peptides, we synthesized and evaluated immunomodulatory activity of four peptidomimetic compounds, i.e. Tyr-NH-C(Me)(2)-CH(2)-O-Phe-NH(2 )(1), Tyr-NH-C(6)H(5)-(o)-CH(2)-CH(2)-O-Phe-NH(2) (2), Tyr-NH-CH(2)-CH(2)-O-Phe-NH(2) (3) and Tyr-NH-CH(D-Et)-CH(2)-O-Phe-NH(2) (4). METHODS: These compounds were synthesized in solution phase and evaluated for their immunomodulatory properties in vitro by mixed lymphocyte reaction (MLR), proliferation of opioid receptor-expressing cells, production of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide. RESULTS: This study shows the immunosuppressive potential of synthetic peptidomimetic compound 3. This compound inhibited two-way MLR and suppressed the proliferation of the mu-opioid receptor expressing human embryonic kidney cells HEK 293 in vitro. Inhibition of MLR by compound 3 was reversed by naloxone (opioid receptor antagonist) and beta-funaltrexamine hydrochloride (mu-opioid receptor antagonist). The immunosuppressive effect of compound 3 was further demonstrated by inhibition of TNF-alpha and nitric oxide production in lipopolysaccharide-stimulated human PBMCs and mouse macrophage cells RAW 264.7, respectively. CONCLUSION: These observations suggest that compound 3 inhibits MLR through mu-opioid receptor present on cells.

Animals↗

PubMed1993

Immunomodulation of human T cell responses with receptor selective enkephalins.

The delta-opioid receptor selective [2-D-penicillamine-5-D-penicillamine] enkephalin (DPDPE) and the mu receptor selective Tyr-D-Orn-Phe-Asp-NH2 (TOPA) were found respectively, to have marked immunostimulant and immunosuppressant activities in both normal subjects and patients suffering from leprosy and tuberculosis. Antigen specific lymphoproliferation and numbers of rosette forming T cells were significantly (P < 0.05) enhanced on in vitro treatment with Met-enkephalin. This was further increased (P < 0.001) in the presence of the delta selective DPDPE. In contrast, treatment with mu selective TOPA inhibited lymphoproliferation substantially (P < 0.01) and rosette formation to a lesser extent.

Adjuvants, Immunologic↗

PubMed1989

Morphine-like activity of some N-substituted amides of met-enkephalin.

Opioid activity of a homologous series of met-enkephalin alkylamides was analysed. In guinea pig ileum test, the hexylamide derivative was most active, whereas the isopropylamide derivative was most potent in analgesia test. The results suggest that structural changes of this type at the C-terminus of the pentapeptide improve the opioid activity.

Amides↗

PubMed1988

Human interferon-gamma protects rhesus monkeys against sporozoite-induced Plasmodium cynomolgi malaria infection.

Earlier we reported that prophylactic treatment with recombinant human interferon gamma (rHuIFN-gamma) for a prolonged duration completely suppressed experimental infection with Plasmodium cynomolgi B sporozoites in rhesus monkeys. We now show that reducing the rHuIFN-gamma treatment to three administrations given close to the time (on days -1, 0, and +1) of infection was sufficient for complete protection. Animals initially protected by rHuIFN-gamma treatment are susceptible to reinfection. Studies are in progress to understand the precise mechanism of protection afforded by HuIFN-gamma against sporozoite-induced malaria infection.

Animals↗

PubMed1977