Anti-IL6 polyclonal antibody [Biotin]

Resolvins, a new family from the endogenous specialized pro-resolving mediators (SPMs), promote the resolution of the inflammatory response. Resolvin D3 (RvD3), a docosahexaenoic acid (DHA) product, has been known to suppress the inflammatory response. However, the anti-inflammatory and neuroprotective effects of RvD3 are not known in a model of spinal cord injury (SCI). Here, we investigated the anti-inflammatory and neuroprotective effect of RvD3 in a mouse model of SCI. Processes associated with anti-inflammation and angiogenesis were studied in RAW 264.7 cells and the human brain endothelial cell line hCMEC/D3, respectively. Additionally, female C57BL/6 mice were subjected to moderate compression SCI (20-g weight compression for 1 min) followed by intrathecal injection of vehicle or RvD3 (1 mu g/20 mu L) at 1 h post-SCI. RvD3 decreased the lipopolysaccharide (LPS)-induced production of inflammatory mediators and nitric oxide (NO) in RAW 264.7 cells and promoted an angiogenic effect in the hCMEC/D3 cell line. Treatment with RvD3 improved locomotor recovery and reduced thermal hyperalgesia in SCI mice compared with vehicle treatment at 14 days post-SCI. Remarkably, RvD3-treated mice exhibited reduced expression of inflammatory cytokines (TNF-alpha, IL6, IL1 beta) and chemokines (CCL2, CCL3). Also, RvD3-treated mice exhibited increased expression of tight junction proteins such as zonula occludens (ZO)-1 and occludin. Furthermore, immunohistochemistry showed a decreased level of gliosis (GFAP, Iba-1) and neuroinflammation (CD68, TGF-beta) and enhanced neuroprotection. These data provide evidence that intrathecal injection of RvD3 represents a promising therapeutic strategy to promote inflammatory resolution, neuroprotection, and neurological functional recovery following SCI.

Peptidoglycan recognition protein 3 (PGlyRP3) is a pattern recognition protein found in the gut epithelia and proven to have an anti-inflammatory effect in response to dietary lipids via the upregulation of PPAR gamma. We have reported an in vitro anti-inflammatory action for prebiotic oligosaccharides in the intestinal Caco-2 cells through stimulation of PPAR gamma and PGlyRP3. In the present study, this effect was examined in vivo in a DSS-induced colitis mouse model. Both Raftilose P95 and alpha 3-Sialyllactose oligosaccharides upregulated PGlyRP3 and showed an anti-colitis effect as evidenced by increased survival and reductions in body weight loss, bleeding in stool, diarrhea, and the expression of the cytokine genes IL6, IL1b and TNF alpha. However, unlike the in vitro results, the role of PPAR gamma was unclear; both oligosaccharides could upregulate neither PPAR gamma gene nor protein expressions, nor the administration of its inhibitor BADGE could affect the upregulation of PGlyRP3 in response to oligosaccharides. Instead, phosphoimmunoblotting indicated that both oligosaccharides inhibit the phosphorylation of MEK1/2 and ERK1/2 caused by DSS. Also, both oligosaccharides reversed the DSS-induced downregulation in the gene expression of I kappa B alpha, the upregulation of NF kappa B1 and cox2, and the decrease of the cytoplasmic (inactive) NF-kappa B p65 protein that indicates its transformation to the (active) inflammatory nuclear form. The present study showed that the prebiotic oligosaccharides Raftilose P95 and alpha 3-Sialyllactose have an anti-colitis effect in mice through the induction of PGlyRP3 expression and down-regulation of the MEK/ERK and the NF-kappa B inflammatory pathways.