Nimesulide inhibits lipopolysaccharide-induced production of superoxide anions and nitric oxide and iNOS expression in alveolar macrophages

Khanduja, Krishan Lal; Sohi, Kiranjit Kaur; Pathak, Chander Mohan; Kaushik, Gaurav

doi:10.1016/j.lfs.2005.07.033

Cited by 27 publications

(13 citation statements)

References 35 publications

(35 reference statements)

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“…Data showing that a COX-2 inhibitor attenuated LPS-induced iNOS/NO are consistent with this autocrine loop being operative in rat AMs as well (31). Neither of these reports, however, established that PGE 2 was the pros- tanoid responsible for potentiating LPS-induced NO.…”

Section: Discussionmentioning

confidence: 60%

Distinct Protein Kinase A Anchoring Proteins Direct Prostaglandin E2 Modulation of Toll-like Receptor Signaling in Alveolar Macrophages

Kim

Serezani

Okunishi

et al. 2011

Journal of Biological Chemistry

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Toll-like receptors (TLRs) direct a proinflammatory program in macrophages. One mediator whose generation is induced by TLR ligation is prostaglandin E 2 (PGE 2 ), which is well known to increase intracellular cAMP upon G protein-coupled receptor ligation. How PGE 2 /cAMP shapes the nascent TLR response and the mechanisms by which it acts remain poorly understood. Here we explored PGE 2 /cAMP regulation of NO production in primary rat alveolar macrophages stimulated with the TLR4 ligand LPS. Endogenous PGE 2 synthesis accounted for nearly half of the increment in NO production in response to LPS. The enhancing effect of PGE 2 on LPS-stimulated NO was mediated via cAMP, generated mainly upon ligation of the E prostanoid 2 receptor and acting via protein kinase A (PKA) rather than via the exchange protein activated by cAMP. Isoenzyme-selective cAMP agonists and peptide disruptors of protein kinase A anchoring proteins (AKAPs) implicated PKA regulatory subunit type I (RI) interacting with an AKAP in this process. Gene knockdown of potential RI-interacting AKAPs expressed in alveolar macrophages revealed that AKAP10 was required for PGE 2 potentiation of LPS-induced NO synthesis. AKAP10 also mediated PGE 2 potentiation of the expression of cytokines IL-10 and IL-6, whereas PGE 2 suppression of TNF-␣ was mediated by AKAP8-anchored PKA-RII. Our data illustrate the pleiotropic manner in which G protein-coupled receptor-derived cAMP signaling can influence TLR responses in primary macrophages and suggest that AKAP10 may coordinate increases in gene expression.Tissue macrophages play a pivotal role in innate immune responses. Via recognition receptors such as Toll-like receptors (TLRs), 3 these sentinel cells sense pathogens and other danger signals and then initiate a coordinated inflammatory response (1). The best-studied example is the recognition by TLR4 of LPS of Gram-negative bacterial cell walls. TLR-mediated inflammation is orchestrated by the activation of transcription factors including NFB (2). NFB-dependent genes that are critical to antimicrobial defense include proinflammatory cytokines and iNOS (3). NO is an important signaling molecule involved in regulating a wide range of biological activities in the neural, vascular, and immune systems. NO and its metabolites mediate a number of host defense functions of activated macrophages, including antimicrobial and tumoricidal activities, but are also implicated in the pathogenesis of tissue damage associated with acute and chronic inflammation (4).Ligation of TLRs also enhances the expression of COX-2, the enzyme responsible for the inducible generation of prostanoids including prostaglandin E 2 (PGE 2 ) (5, 6). PGE 2 is produced in abundance at sites of inflammation and infection and itself modulates many aspects of macrophage function (7). The immunomodulatory effects of PGE 2 largely result from its ability to increase intracellular cAMP through the stimulatory G protein (G s )-coupled E prostanoid (EP) receptors EP2 and EP4 (8). Increases in intracellular cA...

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Section: Discussionmentioning

confidence: 60%

Distinct Protein Kinase A Anchoring Proteins Direct Prostaglandin E2 Modulation of Toll-like Receptor Signaling in Alveolar Macrophages

Kim

Serezani

Okunishi

et al. 2011

Journal of Biological Chemistry

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“…Guggulipid and nimesulide have significantly inhibited the LPS stimulated NO release in C6 cells which depicts the beneficial role of these drugs in NO mediated neuroinflammatory disorders. Reports have described that guggulsterones (Meselhy, 2003) and nimesulide (Khanduja et al, 2006) inhibit LPS induced nitrite production in macrophages also give the strong support on the NO inhibiting potential of these drugs. Elevated oxidative stress (ROS generation, MDA formation and GSH deficit) in activated astroglial cells is main event in neuroinflammation and important cause of neuronal cell death in neurodegenerative diseases and CNS disorders (Stepananko et al, 2000).…”

Section: Discussionmentioning

confidence: 89%

Evaluation of guggulipid and nimesulide on production of inflammatory mediators and GFAP expression in LPS stimulated rat astrocytoma, cell line (C6)

Niranjan

Kamat

Nath

et al. 2010

Journal of Ethnopharmacology

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“…In addition, NO is a highly reactive ROS molecule that may act as a double edged sword and involved in the regulation of physiological and pathophysiological mechanisms in the cardiovascular, nervous and immunological systems. 36) The prolonged production of NO may act as a cytotoxic agent in pathological conditions such as inflammation, infection, neoplastic disease, liver cirrhosis and diabetes. 37,38) Therefore, the selective inhibition of NO production in inflammatory cells, such as macrophages, may offer a new therapeutic strategy against inflammation.…”

Section: Discussionmentioning

confidence: 99%

Component and Antioxidant Properties of Polysaccharide Fractions Isolated from Angelica sinensis (OLIV.) DIELS

Yang

Zhao

Yan-juan

et al. 2007

Biological & Pharmaceutical Bulletin

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Oxidative stress is thought to play a key role in macrophage foam cell formation which is the hallmark of the early atherosclerotic lesion. 1,2) Oxidative stress is associated with lipid peroxidation in lipoproteins and in arterial cells, including macrophages.3,4) These "oxidized macrophages" are characterized by increased peroxide levels, decreased glutathione content, and increased capability to oxidize lowdensity lipoprotein. 5,6) These properties of the cells increase their capability to accumulate cholesterol and to form macrophage foam cells. 7,8) Antioxidants can reduce the cellular oxidative stress by inhibiting the formation of superoxide anions, and by detoxification of reactive oxygen species/reactive nitrogen species through upregulation of cellular defense mechanisms, such as superoxide dismutase, catalase, or glutathione peroxidase. 9,10) Naturally occurring antioxidants in plants are classified as vitamins, phenolic compounds, tannins, volatile compounds and so on. Among them, herbs have received much attention as preventive medicines and ingredients in a variety of processed foods because they have beneficial health effects such as antioxidant and antibacterial activity.11) In recent years, polysaccharides from plant origin have also emerged as a relevant class of bioactive natural products and the great advances have been made in chemical and biological studies of natural polysaccharides as new safe plant-based health foods. 12-15)Angelica sinensis (OLIV.) DIELS is a herbaceous perennial plant mainly distributed in the northwest of China. The root is variously called Dang Gui or Dong Quai. It has been traditionally applied to the treatment of gynecological disorders (e.g., menstrual disorders, amenorrhea, dysmenorrhea, anemia, premenstrual syndrome, menopause) for thousands of years in Asia. 16,17) It was first introduced into the West in 1899 by Merck in the form of a liquid extract named "Eumenol" and was presently marketed in the United States as a dietary supplement, with numerous products being marketed worldwide. 18,19) In recent years, it was also reported that the polysaccharide extracts from A. sinensis possessed significant immunomodulatory activity. 20) However, it is not known whether A. sinensis polysaccharides have any direct antioxidant effects and more detailed work is needed on the elucidation of the sugar composition and antioxidant activities of active polysaccharides.In the present study, we isolated and purified three A. sinensis polysaccharide fractions (APFs), designed as APF1, APF2 and APF3 from the roots of A. sinensis and the antioxidant activities of APFs against hydrogen peroxide (H 2 O 2 )-mediated oxidative stress were evaluated in isolated mouse peritoneal macrophages. Furthermore, the sugar composition in APFs was also characterized by high-performance capillary electrophoresis (HPCE). Sciences, Shaanxi Normal University; Xi'an 710062, China: and b Faculty of Pharmaceutical Sciences, Fourth Military Medical University; Xi'an 710032, China. Received March 30, ...

show abstract

Nimesulide inhibits lipopolysaccharide-induced production of superoxide anions and nitric oxide and iNOS expression in alveolar macrophages

Cited by 27 publications

References 35 publications

Distinct Protein Kinase A Anchoring Proteins Direct Prostaglandin E2 Modulation of Toll-like Receptor Signaling in Alveolar Macrophages

Distinct Protein Kinase A Anchoring Proteins Direct Prostaglandin E2 Modulation of Toll-like Receptor Signaling in Alveolar Macrophages

Evaluation of guggulipid and nimesulide on production of inflammatory mediators and GFAP expression in LPS stimulated rat astrocytoma, cell line (C6)

Component and Antioxidant Properties of Polysaccharide Fractions Isolated from Angelica sinensis (OLIV.) DIELS

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