title: Cross-talk between NO and arachidonic acid in inflammation.
abstract: Inducible nitric oxide synthase (iNOS) is expressed in a variety of cell types, in particular in inflammatory cells, in response to diverse pro-inflammatory stimuli. This process requires critical levels of arachidonic acid (AA), generated by constitutive phospholipase A(2) (PLA(2)), promoting tyrosine kinase-dependent phosphorylation, and inhibition, of constitutive NOS. Lowering basal NO levels is indeed critical for the activation of nuclear factor-kappaB (NF-kappaB), and thus for the expression of genes (e.g. iNOS) regulated by this transcription factor. It is interesting to note that NO and AA, two small lipid soluble molecules, rapidly cross the plasma membrane thereby allowing the triggering of the above responses in distal cells. That is, constitutive NO might inhibit NF-kappaB activity in the same cells (e.g. astrocytes) in which it is generated, as well as in other cells that do not express constitutive NOS (e.g. microglia). NO from cells unable to respond to pro-inflammatory stimuli (e.g. neurons) will also contribute to these effects. Along the same line, AA released by pro-inflammatory molecules in specific cell types (e.g. astrocytes) might suppress constitutive NOS activity in the same cells as well as in other cells (e.g. neurons). Thus, AA produced at the very early stages of the inflammatory response is a likely critical signal switching the regulation of the "NO tone" from physiological (i.e. mediated by constitutive NOS) to pathological (i.e. mediated by iNOS). This second phase of the inflammatory response is often accompanied by the onset of deleterious effects in the tissue in which a critical role is played by iNOS-derived NO (directly or indirectly, i.e. via formation of peroxynitrite) as well as by products of the AA cascade. In summary, we suggest that the relative amounts of NO and AA, released by their constitutive enzymes, produce autocrine and paracrine effects regulating the onset of an inflammatory response in which, in addition to other factors, NO and AA are extensively released by their inducible enzymes.
authors: Department of Morphologic and Biomedical Sciences, University of Verona, Verona, Italy. sofia.mariotto@medicina.univr.it
authors: Sofia
authors: S
authors: Mariotto
authors: Ylenia
authors: Y
authors: Suzuki
authors: Tiziana
authors: T
authors: Persichini
authors: Marco
authors: M
authors: Colasanti
authors: Hisanori
authors: H
authors: Suzuki
authors: Orazio
authors: O
authors: Cantoni
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D050356:Lipid Metabolism / Q000502:physiology; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
chemical_list: D016328:NF-kappa B; D014157:Transcription Factors; D016718:Arachidonic Acid; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D011505:Protein-Tyrosine Kinases; D010741:Phospholipases A