Proteolysis of acute phase proteins: Implication to the anti-inflammatory response

Peptides ◽  
1992 ◽  
pp. 879-880
Author(s):  
O. Rosen ◽  
P. Landsmann ◽  
M. Pras ◽  
D. Levartowsky ◽  
M. Pontet ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Anti Inflammatory

Inflammation: a role for NR4A orphan nuclear receptors?

2011 ◽  
Vol 39 (2) ◽  
pp. 688-693 ◽  
Author(s):  
Jason P. McMorrow ◽  
Evelyn P. Murphy
Keyword(s):  
Inflammatory Response ◽  
Nuclear Receptors ◽  
Acute Phase ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Acute Phase Proteins ◽  
Tissue Injury ◽  
Chronic Phase ◽  
Psoriatic Skin ◽  
Orphan Nuclear Receptors

Inflammation is paradoxical; it is essential for protection following biological, chemical or physical stimuli, but inappropriate or misdirected inflammation is responsible for tissue injury in a variety of inflammatory diseases. The polarization of immune cells is critical in controlling the stages of inflammatory response. The acute phase of inflammation is characterized by a T-lymphocyte:Th2 cytokine profile and involves a co-ordinated migration of immune cells to the site of injury where production of cytokines and acute-phase proteins brings about healing. However, persistent inflammation can result in inappropriate and prolonged T-lymphocyte:Th1 cytokine-mediated action and reaction of self-molecules, leading to a chronic phase in diseases such as RA (rheumatoid arthritis), Ps (psoriasis) and atherosclerosis. The inflammatory response is also controlled by activated macrophage cells, with classically activated (M1) cells producing a wide variety of pro-inflammatory mediators, while alternatively activated (M2) macrophages participate in anti-inflammatory response. Members of the NR4A subfamily (NR4A1/NUR77, NR4A2/NURR1 and NR4A3/NOR1) of orphan NRs (nuclear receptors) have emerged as key transcriptional regulators of cytokine and growth factor action in diseases affecting our aging population. As ligand-independent and constitutively active receptors, the activity of these transcription factors is tightly controlled at the level of expression, post-translational modification and subcellular localization. NR4A subfamily members are aberrantly expressed in inflamed human synovial tissue, psoriatic skin, atherosclerotic lesions, lung and colorectal cancer cells. Significantly, prolonged or inappropriate inflammatory responses contribute to the pathogenesis of these diseases. In activated cells, NR4A receptors are rapidly and potently induced, suggesting that these receptors may act as important transcriptional mediators of inflammatory signals. NR4A receptors may contribute to the cellular processes that control inflammation, playing a critical part in the contribution of chronic inflammation or they may have a protective role, where they may mediate pro-resolution responses. Here, we will review the contribution of the NR4A orphan NRs to integration of cytokine signalling in inflammatory disorders.

scholarly journals Clinical Efficacy of Antimicrobial Agents in Combination with Flunixin Meglumine and Phenylbutazone on Acute Phase Response in Respiratory Disease of Calves

2021 ◽  
Vol 41 (01) ◽  
pp. 71-77
Author(s):  
Wael M. El-Deeb
Keyword(s):  
Respiratory Disease ◽  
Acute Phase ◽  
Antimicrobial Agents ◽  
Acute Phase Proteins ◽  
Interleukin 8 ◽  
Response To Treatment ◽  
Amyloid A ◽  
Flunixin Meglumine ◽  
Histophilus Somni ◽  
Anti Inflammatory

The aim of this study was to correlate the serum levels of acute phase proteins (APPs) and cytokines in response to treatment by various antimicrobial agents in feedlots calves (FL) naturally infected with Mannheimia haemolytica (M. haemolytica) and Histophilus somni (H. somni). 840 feedlot calves in one farm in Al-Kharg region, Saudi Arabia were clinically examined for the presence of respiratory disease manifestations. The infection was confirmed using nasopharyngeal swabs. Blood samples from diseased animals were collected before and after (7 days) treatment for biochemical analysis of serum amyloid A (SAA), haptoglobin (HP) and cytokines tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin-1 β (IL1β), and interleukin-8 (IL-8). FL that were positive for M. haemolytica and/or H. somni (n=69) received treatment with one antibiotic, including tulathromycin (Tula; n=26 cases), florfenicol (FFC; n=19), tilmicosin (Tm; n=13), or ceftiofur (CEF; n=11) and one non-steroidal anti-inflammatory drug (Flunixin meglumine (FM; n=43) or phenylbutazone (PBZ; n= 26). We demonstrated the selective potent inhibitory effect of the administrated anti-inflammatory agents either FM or PBZ on the production of APPs and pro-inflammatory cytokines in FL infected with bovine respiratory disease (BRD). Our findings showed the antibacterial efficacy of FFC and Tm for the treatment of infected FL when administrated with either FM or PBZ. However, Tula was preferable to administrate in combination with FM for the treatment of FL with respiratory manifestations. Importantly, monitoring the sera level of Hp, IL-1β, and interleukin-8 (IL-8) in feedlots treated with either FM combined with Tula, FFC, or Tm or PBZ combined with FFC, and Tm has been effective in predicting the disease prognosis

PPARγ Regulates the Anti-Inflammatory Effects of Carbon Monoxide on Macrophages: A Gene Profiling Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3445-3445
Author(s):  
Martin Bilban ◽  
Sherrie L. Otterbein ◽  
Emeka Ifedigbo ◽  
Keiji Enjyoji ◽  
Anny Usheva ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Inflammatory Response ◽  
Acute Phase Proteins ◽  
Expression Patterns ◽  
Endotoxic Shock ◽  
Gene Profiling ◽  
In Vivo Experiments ◽  
Anti Inflammatory

Abstract Carbon monoxide (CO) at low concentrations has generated recent interest due to its ability to modulate the inflammatory response associated with chronic graft rejection, vascular injury and septic shock. Both in vivo and in vitro CO can inhibit the expression of pro-inflammatory genes such as TNFα in macrophages while simultaneously increasing the expression of the anti-inflammatory cytokine IL-10. The mechanisms by which this occurs are still unclear. To better understand the mechanisms underlying the effects of CO, we employed the Affymetrix GeneChip technology to evaluate the time-dependent expression patterns of >12,000 genes in macrophages stimulated with bacterial endotoxin (LPS) in the presence or absence of a low concentration of CO previously demonstrated to evoke an anti-inflammatory response. We were particularly interested whether CO would, by itself, modulate in a specific manner the expression of proteins that might explain the anti-inflammatory effects observed following subsequent administration of endotoxin. RAW 264.7 murine macrophages were grown to 75% confluency and then exposed to CO (250 ppm) for 3 hr prior to administration of LPS (10 ng/ml). At 0, 15, 30, 60, 120 and 240 min thereafter, total RNA was isolated by standard methods and the RNA was then labeled and hybridized to U74Av2 GeneChips. Of >12,000 genes assessed, 116 of 270 that were LPS-responsive were affected by CO treatment. CO inhibited the majority of LPS-induced pro-inflammatory cytokines and acute phase proteins including expression of early growth response-1 (Egr-1), a transcription factor that serves as a central intermediary regulating many genes. Egr-1 was nearly completely inhibited by CO as was Egr-1-dependent expression of tissue factor (TF) and PAI-1. Treatment of cells with CO alone led to a rapid early increase in PPARγ, the expression of which was essential for the anti-inflammatory effects of CO. Inhibition of PPARγ using the selective chemical inhibitor GW9662 reversed the CO inhibitory effects on LPS-induced Egr-1 and TF expression. Correlative in vivo experiments in mice showed that CO pre-treatment blocked endotoxin-induced Egr-1 expression and decreased markers of lung inflammmation the effects of which were also lost with inhibition of PPARγ. Our analyses of gene expression patterns has led to the first molecular understanding of how treatment with CO, in this case by inducing PPARγ, blocks the pro-inflammatory response. These experiments provide novel insights into the mechanisms and pathophysiology of endotoxic shock and identify cellular targets by which CO mediates these cytoprotective effects.

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