phycocyanobilin and Inflammation

The antinociceptive and pharmacological activities of C-Phycocyanin (C-PC) and Phycocyanobilin (PCB) in the context of inflammatory arthritis remain unexplored so far. In the present study, we aimed to assess the protective actions of these compounds in an experimental mice model that replicates key aspects of human rheumatoid arthritis.. Antigen-induced arthritis (AIA) was established by intradermal injection of methylated bovine serum albumin in C57BL/6 mice, and one hour before the antigen challenge, either C-PC (2, 4, or 8 mg/kg) or PCB (0.1 or 1 mg/kg) were administered intraperitoneally. Proteome profiling was also conducted on glutamate-exposed SH-SY5Y neuronal cells to evaluate the PCB impact on this key signaling pathway associated with nociceptive neuronal sensitization.. C-PC and PCB notably ameliorated hypernociception, synovial neutrophil infiltration, myeloperoxidase activity, and the periarticular cytokine concentration of IFN-γ, TNF-α, IL-17A, and IL-4 dose-dependently in AIA mice. In addition, 1 mg/kg PCB downregulated the gene expression for T-bet, RORγ, and IFN-γ in the popliteal lymph nodes, accompanied by a significant reduction in the pathological arthritic index of AIA mice. Noteworthy, neuronal proteome analysis revealed that PCB modulated biological processes such as pain, inflammation, and glutamatergic transmission, all of which are involved in arthritic pathology.. These findings demonstrate the remarkable efficacy of PCB in alleviating the nociception and inflammation in the AIA mice model and shed new light on mechanisms underlying the PCB modulation of the neuronal proteome. This research work opens a new avenue to explore the translational potential of PCB in developing a therapeutic strategy for inflammation and pain in rheumatoid arthritis.

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Cytokines; Gene Expression; Humans; Inflammation; Mice; Mice, Inbred C57BL; Neuroblastoma; Neutrophil Infiltration; Nociception; Pain; Phycocyanin; Proteome

The main limitation to successful transplantation is the antigraft response developed by the recipient immune system, and the adverse side effects of immunosuppressive agents which are associated with significant toxicity and counter indications such as infection and cancer. Furthermore, immunosuppressants do little to prevent ischemia-reperfusion injury during the transplantation procedure itself hence there is a growing need to develop novel immunosuppressive drugs specifically aimed at prolonging graft survival. Linear tetrapyrroles derived from the breakdown of mammalian heme have been shown in numerous studies to play a protective role in allograft transplantation and ischemia-reperfusion injury; however, commercial sources of these products have not been approved for use in humans. Plants and algae produce equivalent linear tetrapyrroles called bilins that serve as chromophores in light-sensing. One such marine-derived tetrapyrrole, phycocyanobilin (PCB), shows significant structural similarity to mammalian biliverdin (BV) and may prove to be a safer alternative for use in the clinic if it can exert direct effects on human immune cells. Using a mixed lymphocyte reaction, we quantified the allogeneic responses of recipient cells to donor cells and found that PCB, like BV, effectively suppressed proliferation and proinflammatory cytokine production. In addition, we found that BV and PCB can directly downregulate the proinflammatory responses of both innate dendritic cells and adaptive T cells. We therefore propose that PCB may be an effective therapeutic drug in the clinical setting of transplantation and may also have wider applications in regulating inappropriate inflammation.

Topics: Animals; Antioxidants; Biliverdine; CD3 Complex; CD4-Positive T-Lymphocytes; Cell Proliferation; Cytokines; Dendritic Cells; Female; Humans; Immunosuppressive Agents; Inflammation; Lymphocyte Activation; Mice, Inbred C57BL; Phycobilins; Phycocyanin; Reperfusion Injury; T-Lymphocytes, Regulatory; Tetrapyrroles; Th1 Cells; Transplantation, Homologous

Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H2O2 and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed.

Topics: Animals; Biomarkers; Brain Chemistry; Cell Survival; Cerebrovascular Disorders; Coloring Agents; Cytokines; Genes, MHC Class II; Glutamic Acid; Hydrogen Peroxide; Inflammation; Male; Microarray Analysis; Oxidation-Reduction; Oxidative Stress; PC12 Cells; Phycobilins; Phycocyanin; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Spirulina; Tetrazolium Salts; Thiazoles; Vascular Endothelial Growth Factor A

The most foolproof way to promote survival in epidemics of potentially lethal influenza is to target, not highly mutable viral proteins, but rather intracellular signaling pathways which promote viral propagation or lung inflammation. NF-kappaB, activated in influenza-infected lung epithelial cells and macrophages, is one likely target in this regard, as it plays a role both in viral replication and in the excessive lung inflammation often evoked by influenza infection. Indeed, salicylates, which suppress NF-kappaB activation, have been shown to reduce the lethality of H5N1 avian-type influenza in mice. Another potential target is NADPH oxidase, as this may be a major source of influenza-evoked oxidant stress in lung epithelial cells as well as in phagocytes attracted to lung parenchyma. A number of studies demonstrate that oxidant stress contributes to overexuberant lung inflammation and lethality in influenza-infected mice. The documented utility of N-acetylcysteine, a glutathione precursor, for promoting survival in influenza-infected mice, and diminishing the severity of influenza-like infections in elderly humans, presumably reflects a key role for oxidative stress in influenza. The lethality of influenza is also reduced in mice pretreated with adenovirus carrying the gene for heme oxygenase-1; this benefit may be mediated, at least in part, by the ability of bilirubin to inhibit NADPH oxidase. It may be feasible to replicate this benefit clinically by administering biliverdin or its homolog phycocyanobilin, richly supplied by spirulina. If this latter speculation can be confirmed in rodent studies, a practical and inexpensive regimen consisting of high-dose salicylates, spirulina, and N-acetylcysteine, initiated at the earliest feasible time, may prove to have life-saving efficacy when the next killer influenza pandemic strikes.

Topics: Animals; Birds; Disease Outbreaks; Gene Expression Regulation, Enzymologic; Humans; Inflammation; Influenza in Birds; Influenza, Human; Lung; Macrophages; Mice; Models, Theoretical; NADPH Oxidases; NF-kappa B; Phycobilins; Phycocyanin; Signal Transduction