title: Modulation of LPS induced inflammatory response by Lawsonyl monocyclic terpene from the marine derived Streptomyces sp.
abstract: In continuing research for compounds with immunosuppressive activity, Lawsonone (1), a novel Lawsonyl derivative isolated from marine-derived bacteria Streptomyces sp. was evaluated for its potent immunosuppressive activity on immune system. The effect of Lawsonone (1) was elucidated on the immune cells (splenocytes and macrophages) collected from BALB/c mice. Study was carried out to find the effect of Lawsonone (1) on Con-A and LPS stimulated splenocyte proliferation, LPS-induced NO, IL-1β, IL-6 and TNF-α production in macrophages. Furthermore, the effect of Lawsonone (1) on T-cell subsets (CD4 and CD8) and total B-cell (CD19) population was analyzed by flow cytometry. The results obtained in the present study showed that Lawsonone (1) inhibited the proliferation of both T and B splenocytes. It inhibited the nitric oxide (NO) and pro-inflammatory cytokine (IL-1β, IL-6 and TNF-α) production in LPS-stimulated macrophages in a dose-dependent manner. Moreover, flow cytometric analysis indicated the prominent inhibition of CD4, CD8 and CD19 cell populations in the spleen of mice treated with the variable doses of Lawsonone (1), with the maximum inhibition at the lowest dose (0.1μM). Taken together, the present results suggest that Lawsonone (1) may act as a potent molecule for immunosuppression and anti-inflammation, supporting its immunopharmacologic application to modify the immune system.
authors.affiliation: Natural Product Chemistry Division, Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. asifchem73@gmail.com
authors.forename: Asif
authors.initials: A
authors.lastname: Ali
authors.forename: Anamika
authors.initials: A
authors.lastname: Khajuria
authors.forename: Tabasum
authors.initials: T
authors.lastname: Sidiq
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Narsinh L
authors.initials: NL
authors.lastname: Thakur
authors.forename: Deepak
authors.initials: D
authors.lastname: Naik
authors.forename: Ram A
authors.initials: RA
authors.lastname: Vishwakarma
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology*; D016130:Immunophenotyping; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013302:Streptomyces / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D039821:Monoterpenes; D009569:Nitric Oxide