title: Hypothesis: an alternative pathway for the regulation of inflammation.
abstract: Regulation of inflammation is a crucial event since its alteration, such as in sepsis and chronic autoimmune (i.e. rheumatoid arthritis, lupus erythematosus) or infectious diseases (i.e. tuberculosis, leprosy), determines severe tissue damage. Although there is a general consensus that regulation of inflammation results from a balance between proinflammatory and antiinflammatory pathways, we arrived at the conclusion that well known chemoattractants/proinflammatory molecules such as bacterial formyl peptides or immune complexes (IC), could induce, paradoxically, strong antiinflammatory effects. Thus, we demonstrated that N-formyl-methionyl-leucyl-phenylalanine (FMLP) exerted a drastic antiinflammatory effect, inhibiting the secretion of tumor necrosis alpha (TNF-alpha) induced by lipopolysaccharides, a potent TNF-alpha inducer. We also determined that in human neutrophils FMLP and IC induced the downregulation of receptors for the Fc portion of IgG (FcgammaRII and FcgammaRIIIB). Moreover, FMLP inhibited interferon gamma (IFN-gamma)-induced FcgammaRI expression and IC downregulate class II molecules of the major histocompatibility complex on monocytes. Part of these effects were mediated by the release of aspartic-, serin-, or metalloproteases. All these results favor the postulation of a new concept on the regulation of inflammation carried out through an alternative and non conventional pathway, in which a chemoattractant/proinflammatory agent could, under certain circumstances, act as an antiinflammatory molecule.
authors.affiliation: División Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina. isturiz@hematologia.anm.edu.ar
authors.forename: Martín A
authors.initials: MA
authors.lastname: Isturiz
authors.forename: Macarena
authors.initials: M
authors.lastname: Beigier-Bompadre
authors.forename: Paula
authors.initials: P
authors.lastname: Barrionuevo
authors.forename: Fernanda
authors.initials: F
authors.lastname: Alves-Rosa
authors.forename: Marina S
authors.initials: MS
authors.lastname: Palermo
authors.forename: Marisa
authors.initials: M
authors.lastname: Vulcano
mesh_terms: D000936:Antigen-Antibody Complex / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D007371:Interferon-gamma / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000502:physiology
chemical_list: D000936:Antigen-Antibody Complex; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007371:Interferon-gamma