title: Effect of iNOS inhibitor LNMMA along with antibiotics Chloramphenicol or Ofloxacin in murine peritoneal macrophages regulates S.aureus infection as well as inflammation: An in vitro study.
abstract: Death due to sepsis by S. aureus is rapidly increasing because of their potent weaponries against macrophage mediated killing. Macrophages serve as intracellular reservoirs of S. aureus. Although significant resources have been invested during the last decade in new treatments for sepsis, only antibiotic therapy has failed to improve outcomes. Moreover the host pathogen interaction resulted in host cell death triggering inflammation. So, successful therapy requires amalgamation of therapies to delineate pathogen along with providing protection to host cell. With this idea, LNMMA, the iNOS inhibitor is used along with antibiotics Ofloxacin or Chloramphenicol on S. aureus infected mouse peritoneal macrophage. ROS like H2O2, O2-production has been measured. NO inhibition by iNOS inhibitor and antioxidant levels has been analysed. COX2, TLR2 and iNOS expression along with proinflammatory cytokine level was studied. It was found that the use of iNOS inhibitor LNMMA along with antibiotics not only enhances bacterial clearance but also decreases proinflammatory responses in Staphylococcus aureus infected macrophages. Inhibition of TLR2 as well as COX2 has also been found in combined treatment groups. The use of iNOS inhibitor LNMMA plus Ofloxacin or Chloramphenicol pretreatment enhanced bacterial clearance by increasing ROS. Decreases in NO protect the cell from harmful peroxynitril as well as inflammatory damage by changes in iNOS, COX2 activity along with reduced proinflammatory cytokines like TNFα, IFNγ, IL1-β etc. Changes in antioxidant level has been found. This in-vitro realm of augmented bacterial clearance and regulated inflammation may be considered as a novel and important therapeutic intervention.
authors.affiliation: Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, 92 A.P.C. Road, Calcutta 700009, West Bengal, India. Electronic address: somrita.dey23@gmail.com.
authors.forename: Somrita
authors.initials: S
authors.lastname: Dey
authors.affiliation: Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, 92 A.P.C. Road, Calcutta 700009, West Bengal, India. Electronic address: biswa_dev2@yahoo.com.
authors.forename: Biswadev
authors.initials: B
authors.lastname: Bishayi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000975:Antioxidants / Q000378:metabolism; D002701:Chloramphenicol / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015242:Ofloxacin / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D011897:Random Allocation; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000276:immunology / Q000472:pathogenicity; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D016207:Cytokines; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D013481:Superoxides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D002701:Chloramphenicol; D015242:Ofloxacin; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D010100:Oxygen
keywords: Inflammation; LNMMA; Murine peritoneal macrophages; Pro-inflammatory cytokines; Reactive oxygen species; S.aureus