Mediators of Inflammation

Abstract

MAST cell amines, platelet-activating factor (PAF), Inhibition of NO-synthase and thromboxanes and leukotrienes have been shown to be released during nitric oxide-synthase degranulation of rat omentai mast inhibition in the rat intestine. Mast cells in rat ce[ls in vitro isolated omentum (OMCs) or isolated from the rat peritoneal cavity (PMCs) have been used here to investigate the relationship(s) between these agents. N-nitro-L-arginine methyl ester (L-NAME, A.M. Northover cA and B. J. Northover 100 IM) caused some degranulation of OMCs, but no enhancement of histamine release from PMCs. PAF (5 IM) and U46619 (1 IM) degranulated Department of Pharmaceutical Sciences, School of OMCs and enhanced histamine release from PMCs. Pre-treatment of the omentum with Applied Sciences, De Montfort University, Leicester BN52021 (10 IM) inhibited degranulation of LE1 9BH, UK OMCs in response to L-NAME, PAF or U46619. Pretreatment with 1-benzylimidazole (5 or 50 IM) inhibited the effect of L-NAME but not that of CACorresponding AuthorPAF. Indomethacin (1 IM) or sodium nitroprusside (10 IM) also inhibited the effects of L-NAME, but nordihydroguaiaretic acid (30 IM) did not. In PMCs BN52021 inhibited PAF-induced, but not U46619-induced, release of histamine. These results suggest that inhibition of nitric oxidesynthase in the omentum by L-NAME allows thromboxanes to release PAF, which in turn degranulates and releases histamine from OMCs.

Effects of Oral Cysteine, Penicillamine and N-Acetyl-penicillamine on Adjuvant Arthritis in Rats

“…Although the dosage in the latter experiment was intentionally rather high, it was ap preciably less than rats would receive by imbibing water, con taining 1% cysteine, in volumes comparable to that consumed by untreated animals. The apparent increased severity of the disease resulting from cysteine treatment might possibly be due to the fact that cysteine is reported to be a bradykinin potentiator [3,12], and the latter is regarded as one of the mediators of in flammation [14], The fact that PPLO-induced rat polyarthritis responds to oral treatment with cysteine [6,7], while the adjuvant disease does not, may also reflect the fundamental differences in the etiology and nature of these two diseases in rats.…”

Genome-wide association study reveals shared and distinct genetic architecture underlying fatty acid and bioactive oxylipin metabolites in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

“…Chronic inflammation is a pathological feature underlying many chronic diseases, [1][2][3][4][5] and inflammatory responses involve a variety of so-called "inflammatory mediators" that include both signaling proteins (e.g., cytokines, chemokines) and bioactive lipids such as oxylipins. 6 Oxylipins are derived from the oxygenation of precursor mono-and polyunsaturated fatty acids through cascading pathways mediated by cytochrome P450 (CYP), lipoxygenase (LOX), and cyclooxygenase (COX) enzymes, or through other enzymatic and non-enzymatic reactions 7 (Supplementary Figure 1), and play a variety of roles mediating inflammation and oxidative stress. 8,9 Given the role of inflammation in many chronic diseases, there is growing interest in oxylipin-targeted therapies.…”

Leukocytic Mechanisms in Inflammation

“…Inflammation, originally defined by the symptoms and signs of redness, swelling, heat, pain, and loss of function (1), is currently defined from the point of view of mechanism as the response of the body to tissue injury in volving neurological (2), vascular (3), humoral (4)(5)(6), and cellular (7) fac tors. The function of the response is to remove the injurious agent and the products of tissue injury.…”

“…Several are general and multifaceted (16)(17)(18). Others deal with specific aspects of inflammation including biochemical mechanisms and mediators of the in flammatory response (4,11,(19)(20)(21), chemical interactions in and modifica tions of the inflamed tissue (22)(23)(24), the role of tissue mast cells (25)(26)(27)(28)(29)(30), inflammatory cells (31)(32)(33)(34)(35)(36), the role of leukocyte lysosomes (37), immuno logical mechanisms in inflammation (38)(39)(40)(41)(42)(43), and inflammatory aspects of human disease (44)(45)(46)(47). A number of reviews cover the subject of anti-in flammatory agents.…”