cyclic-gmp and Arthritis

This study investigated the effects of the alga lectin Hypnea cervicornis agglutinin (HCA) on rat zymosan-induced arthritis (ZyA). Zymosan (50-500 μg/25 μL) or sterile saline (Sham) was injected into the tibio-tarsal joint of female Wistar rats (180-200 g). Arthritic animals received morphine (4 mg/kg, intraperitoneal), indomethacin (5 mg/kg, intraperitoneal), or 2% lidocaine (100 μL, subcutaneous). HCA (0.3-3 mg/kg) was administered by intravenous route 30 min before or 2 h after zymosan. 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one (ODQ, 4 μg, intra-articular) was given 30 min prior HCA. Hypernociception was measured every hour until 6 h, time in which animals were sacrificed for evaluation of leukocytes of the intra articular fluid and gene expression of TNF-α, IL-1, IL-10, and iNOS in the joint tissues using PCR techniques. Hypernociception was responsive to morphine and indomethacin, and its threshold was not altered by lidocaine. The post-treatment of HCA reduced both hypernociception and leukocyte influx. This antinociceptive effect was abolished either by ODQ and glibenclamide. HCA also reduced gene expression of iNOS and TNF-α. In conclusion, the antinociceptive effect of HCA in ZyA involves cyclic GMP signalization and selective modulation of cytokine expression.

Topics: Analgesics; Animals; Arthritis; Cyclic GMP; Cytokines; Gene Expression; Lectins; Rats; Rats, Wistar; Rhodophyta; Signal Transduction; Zymosan

To investigate the role of heme oxygenase-1 (HO-1), carbon monoxide (CO), and biliverdin (BVD) in the zymosan-induced TMJ arthritis in rats.. Mechanical threshold was assessed before and 4 h after TMJ arthritis induction in rats. Cell influx, myeloperoxidase activity, and histological changes were measured in the TMJ lavages and tissues. Trigeminal ganglion and periarticular tissues were used for HO-1, TNF-α, and IL-1β mRNA time course expression and immunohistochemical analyses. Hemin (0.1, 0.3, or 1 mg kg. Hemin (1 mg kg. HO-1/BVD/CO pathway activation provides anti-nociceptive and anti-inflammatory effects on the zymosan-induced TMJ hypernociception in rats.

Topics: Animals; Arthritis; Biliverdine; Carbon Monoxide; Cyclic GMP; Cytokines; Down-Regulation; Heme Oxygenase-1; KATP Channels; Male; Nociception; Pain Threshold; Peroxidase; Potassium Channel Blockers; Rats; Rats, Wistar; Signal Transduction; Temporomandibular Joint Disorders; Trigeminal Ganglion; Zymosan

Elevated levels of fibronectin (Fn) in articular cartilage have been linked to the progression of both rheumatoid and osteoarthritis. In this study, we examined intracellular events which follow ligation of Fn to its receptor, the integrin alpha5beta1. In addition, we examined the regulatory influence of nitric oxide on these events, since this free radical has been implicated in cartilage degradation. Exposure of chondrocytes to Fn-coated beads resulted in the circumferential clustering of the alpha5beta1 integrin receptor, which was accompanied by the subplasmalemmal assembly of a focal activation complex comprised of F-actin, the tyrosine kinase, focal adhesion kinase (FAK), the ras related G protein rho A, as well as tyrosine-phosphorylated proteins. Treatment with exogenous nitric oxide (NO) or catabolic cytokines which induce nitric oxide synthase blocked the assembly of F-actin, FAK, rho A and tyrosine-phosphorylated proteins while not affecting the total number of beads bound per cell nor the clustering of alpha5beta1 integrin. Use of a cGMP antagonist (Rp-8-Br cGMPS) or cGMP agonist (Sp-cGMPS) either abolished or mimicked the NO effect, respectively. Adherence of chondrocytes to fibronectin enhanced proteoglycan synthesis by twofold (vs. albumin). In addition, basic fibroblast growth factor (FGF) and insulin growth factor (IGF-1) induced proteoglycan synthesis in chondrocytes adherent to Fn but not albumin suggesting a costimulatory signal transduced by alpha5betal and the FGF receptor. Both constitutive and FGF stimulated proteoglycan synthesis were completely inhibited by nitric oxide. These data indicate that the ligation of alpha5beta1 in the chondrocyte induced the intracellular assembly of an activation complex comprised of the cytoplasmic tail of alpha5beta1 integrin, actin, and the signaling molecules rho A and FAK. We show that NO inhibits the assembly of the intracellular activation complex and the synthesis of proteoglycans, but has no effect on the extracellular aggregation of alpha5beta1 integrin. These observations provide a basis by which nitric oxide can interfere with chondrocyte functions by affecting chondrocyte-matrix interactions.

Topics: Actins; Animals; Arthritis; Cartilage; Cattle; Cell Adhesion; Cell Adhesion Molecules; Cell Membrane; Chondrocytes; Cyclic GMP; Cytokines; Extracellular Matrix; Fibronectins; Focal Adhesion Protein-Tyrosine Kinases; GTP-Binding Proteins; Homeostasis; Nitric Oxide; Protein Binding; Protein-Tyrosine Kinases; Proteoglycans; Receptors, Fibronectin; rhoA GTP-Binding Protein; Signal Transduction

The development of adjuvant arthritis induced important modifications in intracellular levels of cyclic AMP and GMP in primary and secondary lymphoid organs: a continuous decrease in cyclic AMP and a biphasic increase in the level of cyclic GMP which correlate well with the onset of the acute phase and the systemization of the disease.

Topics: Animals; Arthritis; Arthritis, Experimental; Cyclic AMP; Cyclic GMP; Lymph Nodes; Mesentery; Rats; Spleen; Thymus Gland