IL-37 expression improves renal function after ischemia and reperfusion in mice model

Renal ischemia is a major problem in the world that lead to renal failure for which no effective treatment is available. Renal ischemia involves a robust inflammatory response, involving up-regulated chemokine expression and leukocyte accumulation, contributes to the mechanism of renal injury and renal failure. IL-37 is a new human cytokine and has an anti-inflammatory function. Currently, it is unknown whether IL-37 suppresses renal inflammatory response to ischemia. We tested the hypothesis that expression of human IL-37 in mouse protects the renal against ischemic injury through suppression of the renal inflammatory response. IL-37 Tg and WT mice were subjected to right renal nephrectomy to induce unilateral model of ischemia the microvascular clamp was positioned around the left renal pedicles. Serum sampling for measurements of TNF-α, IL-1β, Caspase3, MDA, HMGB1, urea and creatinine. Hematoxylin-eosin staining for histological analysis. The resulted data showed that IL-37 has anti-inflammatory effects in renal IRI as evidenced by significant reduction of the inflammatory markers levels TNF-α, IL-1β and HMGB1. IL-37 has potent antioxidant and anti-apoptotic effects with significant reduction in MDA and caspace-3 respectively

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IL-37 expression improves renal function after ischemia and reperfusion in mice model

American Journal of BioMedicine ◽

10.18081/2333-5106/2021.4/224 ◽

2021 ◽

Vol 9 (4) ◽

pp. 207-224

Author(s):

Paloma E. Pinto

Keyword(s):

Renal Failure ◽

Inflammatory Response ◽

Renal Ischemia ◽

Mice Model ◽

Leukocyte Accumulation ◽

Tnf Α ◽

Anti Inflammatory ◽

Apoptotic Effects ◽

Hematoxylin Eosin ◽

Human Cytokine

Renal ischemia is a major problem in the world that lead to renal failure for which no effective treatment is available. Renal ischemia involves a robust inflammatory response, involving up-regulated chemokine expression and leukocyte accumulation, contributes to the mechanism of renal injury and renal failure. IL-37 is a new human cytokine and has an anti-inflammatory function. Currently, it is unknown whether IL-37 suppresses renal inflammatory response to ischemia. We tested the hypothesis that expression of human IL-37 in mouse protects the renal against ischemic injury through suppression of the renal inflammatory response. IL-37 Tg and WT mice were subjected to right renal nephrectomy to induce unilateral model of ischemia the microvascular clamp was positioned around the left renal pedicles. Serum sampling for measurements of TNF-α, IL-1β, Caspase3, MDA, HMGB1, urea and creatinine. Hematoxylin-eosin staining for histological analysis. The resulted data showed that IL-37 has anti-inflammatory effects in renal IRI as evidenced by significant reduction of the inflammatory markers levels TNF-α, IL-1β and HMGB1. IL-37 has potent antioxidant and anti-apoptotic effects with significant reduction in MDA and caspace-3 respectively.

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Anti-Arthritis Effect through the Anti-Inflammatory Effect of Sargassum muticum Extract in Collagen-Induced Arthritic (CIA) Mice

Molecules ◽

10.3390/molecules24020276 ◽

2019 ◽

Vol 24 (2) ◽

pp. 276 ◽

Cited By ~ 5

Author(s):

Hyelin Jeon ◽

Weon-Jong Yoon ◽

Young-Min Ham ◽

Seon-A Yoon ◽

Se Kang

Keyword(s):

Inflammatory Response ◽

Immunohistochemical Analysis ◽

Cartilage Destruction ◽

Sargassum Muticum ◽

Mice Model ◽

Articular Damage ◽

Tnf Α ◽

Anti Inflammatory ◽

Chronic Autoimmune Disease ◽

Necrosis Factor

(1) Background: Rheumatoid arthritis is a chronic autoimmune disease that causes progressive articular damage and functional loss. It is characterized by synovial inflammation that leads to progressive cartilage destruction. For this reason, research on functional foods that reduce the inflammatory response are under progress. (2) Methods: We focused on the anti-inflammatory effects of Sargassum muticum, and confirmed the effect of the extract on the collagen-induced arthritis (CIA) DBA/1J mice model. (3) Results: The extract was given at concentrations of 50, 100, and 200 mg/kg, and the arthritis score and edema volume of the experimental group were significantly different from the CIA group. The level of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were determined in serum and lymphocytes. The expression of these cytokines in the serum remarkably decreased from S. muticum extract (SME)100 mg/kg, and decreased from SME 200 mg/kg in lymphocytes. Also, immunohistochemical analysis of IL-6 and TNF-α in the joints revealed that the inflammatory response was noticeably lower when treated with S. muticum extract. (4) Conclusions: This study provides results of the experiment of S. muticum extract treatment in a mouse model. The treatment was found to contribute to the alleviation of edema and symptoms by reducing the expression of inflammatory cytokines. It was concluded that it may be a useful substance to help in the mitigation of arthritis symptoms.

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TRPV1 Blocker HCRG21 Suppresses TNF-α Production and Prevents the Development of Edema and Hypersensitivity in Carrageenan-Induced Acute Local Inflammation

Biomedicines ◽

10.3390/biomedicines9070716 ◽

2021 ◽

Vol 9 (7) ◽

pp. 716

Author(s):

Oksana Sintsova ◽

Irina Gladkikh ◽

Anna Klimovich ◽

Yulia Palikova ◽

Viktor Palikov ◽

...

Keyword(s):

Transient Receptor Potential ◽

Thermal Hyperalgesia ◽

Control Group ◽

Transient Receptor Potential Vanilloid ◽

Paw Edema ◽

Mice Model ◽

Edema Formation ◽

Sensitivity Experiment ◽

Tnf Α ◽

Anti Inflammatory

Currently the TRPV1 (transient receptor potential vanilloid type 1) channel is considered to be one of the main targets for pro-inflammatory mediators including TNF-α. Similarly, the inhibition of TRPV1 activity in the peripheral nervous system affects pro-inflammatory mediator production and enhances analgesia in total. In this study, the analgesic and anti-inflammatory effects of HCRG21, the first peptide blocker of TRPV1, were demonstrated in a mice model of carrageenan-induced paw edema. HCRG21 in doses of 0.1 and 1 mg/kg inhibited edema formation compared to the control, demonstrated complete edema disappearance in 24 h in a dose of 1 mg/kg, and effectively reduced the productionof TNF-α in both doses examined. ELISA analysis of blood taken 24 h after carrageenan administration showed a dramatic cytokine value decrease to 25 pg/mL by HCRG21 versus 100 pg/mL in the negative control group, which was less than the TNF-α level in the intact group (40 pg/mL). The HCRG21 demonstrated potent analgesic effects on the models of mechanical and thermal hyperalgesia in carrageenan-induced paw edema. The HCRG21 relief effect was comparable to that of indomethacin taken orally in a dose of 5 mg/kg, but was superior to this nonsteroidal anti-inflammatory drug (NSAID) in duration (which lasted 24 h) in the mechanical sensitivity experiment. The results confirm the existence of a close relationship between TRPV1 activity and TNF-α production once again, and prove the superior pharmacological potential of TRPV1 blockers and the HCRG21 peptide in particular.

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Abstract 620: Angiotensin AT2 Receptor Exerts an Anti-inflammatory Response in Lipopolysaccharide-activated THP-1 Macrophages

Hypertension ◽

10.1161/hyp.62.suppl_1.a620 ◽

2013 ◽

Vol 62 (suppl_1) ◽

Author(s):

Isha S Dhande ◽

Tahir Hussain

Keyword(s):

Inflammatory Response ◽

Interleukin 10 ◽

Receptor Expression ◽

Human Macrophage ◽

No Production ◽

At2 Receptor ◽

Tnf Α ◽

Anti Inflammatory ◽

Pre Treatment ◽

Lps Activation

Macrophages have been shown to be an important contributor to the pathogenesis of hypertension and stroke. The angiotensin AT2 receptor (AT2R), which is expressed in macrophages, is known to promote vasodialation, natriuresis and lower inflammation. The goal of the present study was to explore the anti-inflammatory role of AT2R stimulation in human macrophage-like THP-1 cells activated by lipopolysaccharide (LPS). Phorbol 12-myristate 13-acetate (PMA) differentiated macrophage-like THP-1 cells were treated with AT2R agonist C21 (1 μmol/L) for 30 minutes prior to activation with LPS (1 μg/ml). Media and cells were collected after 24 hours and were analyzed for levels of pro- and anti-inflammatory cytokines and proteins. Pre-treatment with C21 resulted in a 4-fold increase (104.8±6.1 vs 406.7±52.3) in anti-inflammatory interleukin-10 (IL-10) production and a 5-fold decrease (3560±237 vs 588.8±15.94) in pro-inflammatory tumor necrosis factor-α (TNF-α) levels in the media in response to LPS. Predictably, LPS resulted in a 6-fold up-regulation of iNOS expression which was prevented with C21 pre-treatment. A modest decrease in the anti-inflammatory macrophage mannose receptor C type 2 (MRC2) expression was detected with LPS treatment. AT2R agonist pre-treatment, however, increased this receptor expression by ~70% after LPS activation. C21 alone also resulted in a 20% increase in MRC2 expression compared to untreated controls. The anti-inflammatory effect of AT2R activation was abolished in the presence of neutralizing IL-10 antibody (1 μg/ml), indicating a central role for IL-10 in mediating the beneficial response to C21 in LPS activated macrophages. Further, inhibition of nitric oxide (NO) by L-NAME prior to C21 pre-treatment also prevented the decrease in TNF-α and increase in IL-10 in response to AT2R agonist, which suggests that the anti-inflammatory response to C21 may be mediated via increase in NO production prior to LPS activation of macrophages. In conclusion, AT2R stimulation may potentially suppress the inflammatory response of macrophages to LPS by shifting the balance from pro- to anti-inflammatory cytokine production and may prove to be beneficial in the control of the inflammatory component of stroke and hypertension.

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Acute renal failure: determinants and characteristics of the injury-induced hyperinflammatory response

AJP Renal Physiology ◽

10.1152/ajprenal.00072.2006 ◽

2006 ◽

Vol 291 (3) ◽

pp. F546-F556 ◽

Cited By ~ 45

Author(s):

Richard A. Zager ◽

Ali C. M. Johnson ◽

Steve Lund ◽

Sherry Hanson

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Lipoteichoic Acid ◽

Heme Oxygenase 1 ◽

Inos Mrna ◽

Chemokine Production ◽

Tnf Α ◽

Tlr2 Ligand ◽

Tlr4 Ligand ◽

Anti Inflammatory

Acute renal failure (ARF) markedly sensitizes mice to endotoxin (LPS), as evidenced by exaggerated renal cytokine/chemokine production. This study sought to further characterize this state by testing the following: 1) does anti-inflammatory heme oxygenase-1 (HO-1) upregulation in selected ARF models prevent this response? 2) Is the ARF hyperresponsive state specifically triggered by LPS? 3) Does excess iNOS activity/protein nitrosylation participate in this phenomenon? and 4) are upregulated Toll receptors involved? Mice with either 1) rhabdomyolysis-induced ARF (massive HO-1 overexpression), 2) cisplatin nephrotoxicity, 3) or HO-1 inhibition (Sn protoporphyrin) were challenged with either LPS (a TLR4 ligand), lipoteichoic acid (LTA; a TLR2 ligand), or vehicle. Two hours later, renal and plasma TNF-α/mRNA, MCP-1/mRNA, renal nitrotyrosine/iNOS mRNA, and plasma cytokines were assessed. Renal TLR4 was gauged by mRNA and Western blot analysis. Both ARF models markedly hyperresponded to both LPS and LTA, culminating in exaggerated TNF-α, MCP-1, and iNOS/nitrotryosine increments. This was despite the fact that HO-1 exerted anti-inflammatory effects. TLR4 levels were either normal (cisplatin), or markedly depressed (∼50%; rhabdomyolysis) in the ARF kidneys, despite the LPS hyperresponsive state. 1) The ARF kidney can hyperrespond to chemically dissimilar Toll ligands; 2) HO-1 does not prevent this response; 3) excess NO/protein nitrosylation can result; and 4) this hyperresponsiveness can be expressed with either normal or reduced renal TLR4 expression. This suggests that diverse signaling pathways may be involved.

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Comparing the effect of intestinal bacteria from rabbit, pig, and chicken on inflammatory response in cultured rabbit crypt and villus

Canadian Journal of Microbiology ◽

10.1139/cjm-2017-0757 ◽

2019 ◽

Vol 65 (1) ◽

pp. 59-67 ◽

Cited By ~ 1

Author(s):

Hong Xiao Cui ◽

Xiu Rong Xu

Keyword(s):

Inflammatory Response ◽

Inflammatory Responses ◽

Intestinal Bacteria ◽

Inflammatory Factors ◽

Rabbit Ileum ◽

Necrosis Factor Alpha ◽

Heat Treated ◽

Tnf Α ◽

Factor Alpha ◽

Anti Inflammatory

Rabbit is susceptible to intestinal infection, which often results in severe inflammatory response. To investigate whether the special community structure of rabbit intestinal bacteria contributes to this susceptibility, we compared the inflammatory responses of isolated rabbit crypt and villus to heat-treated total bacteria in pig, chicken, and rabbit ileal contents. The dominant phylum in pig and chicken ileum was Firmicutes, while Bacteroidetes was dominant in rabbit ileum. The intestinal bacteria from rabbit induced higher expression of toll-like receptor 4 (TLR4) in rabbit crypt and villus (P < 0.05). TLR2 and TLR3 expression was obviously stimulated by chicken and pig intestinal bacteria (P < 0.05) but not by those of rabbit. The ileal bacteria from those three animals all increased the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in crypts and villus (P < 0.05). Chicken and pig ileal bacteria also stimulated the expression of anti-inflammatory factors interferon beta (IFN-β) and IL-10 (P < 0.05), while those of rabbit did not (P > 0.05). In conclusion, a higher abundance of Gram-negative bacteria in rabbit ileum did not lead to more expressive pro-inflammatory cytokines in isolated rabbit crypt and villus, but a higher percentage of Lactobacillus in chicken ileum might result in more expressive anti-inflammatory factors.

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Anti-Inflammatory Effects of Neochlorogenic Acid Extract from Mulberry Leaf (Morus alba L.) Against LPS-Stimulated Inflammatory Response through Mediating the AMPK/Nrf2 Signaling Pathway in A549 Cells

Molecules ◽

10.3390/molecules25061385 ◽

2020 ◽

Vol 25 (6) ◽

pp. 1385 ◽

Cited By ~ 5

Author(s):

Xiao-han Gao ◽

Sun-dong Zhang ◽

Li-tao Wang ◽

Liang Yu ◽

Xue-lian Zhao ◽

...

Keyword(s):

Inflammatory Response ◽

Signaling Pathway ◽

A549 Cells ◽

Morus Alba ◽

Mulberry Leaf ◽

Tnf Α ◽

Nrf2 Signaling Pathway ◽

Acute Pneumonia ◽

Neochlorogenic Acid ◽

Anti Inflammatory

Neochlorogenic acid (nCGA) is a phenolic compound isolated from mulberry leaf (Morus alba L.), which possesses multiple pharmacological activities containing antioxidant and anti-inflammatory effects. However, the role of nCGA in the treatment of acute pneumonia and the underlying molecular mechanism are still unclear. Hence, the aim of study is to investigate the anti-inflammatory properties of nCGA on LPS-stimulated inflammation in A549 cells. In the present study, results reported that nCGA without cytotoxicity significantly reduced the production of TNF-α, IL-6, and NO, and further suppressed the proteins of iNOS, COX2, TNF-α, IL-6 expression. Furthermore, nCGA also inhibited NF-κB activation and blocked MAPKs signaling pathway phosphorylation. In addition, we found nCGA significantly increased the expression of HO-1 via activating the AMPK/Nrf2 signaling pathway to attenuate the inflammatory response, whereas this protective effect of nCGA was reversed by pre-treatment with compound C (C.C, an AMPK inhibitor). Therefore, all these results indicated that nCGA might act as a natural anti-inflammatory agent for the treatment of acute pneumonia.

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Anti-TNF-α Therapy Exerts Intestinal Anti-inflammatory and Anti-Apoptotic Effects After Massive Bowel Resection in a Rat

Journal of Pediatric Gastroenterology and Nutrition ◽

10.1097/mpg.0000000000002876 ◽

2020 ◽

Vol Publish Ahead of Print ◽

Author(s):

Igor Sukhotnik ◽

Yoav Ben-Shahar ◽

Yulia Pollak ◽

Shlomi Cohen ◽

Anat Guz-Mark ◽

...

Keyword(s):

Bowel Resection ◽

Tnf Α ◽

Anti Inflammatory ◽

Apoptotic Effects ◽

Massive Bowel Resection

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CYP2J2 and EETs Protect Against Pulmonary Hypertension with Lung Ischemia-Reperfusion Injury In Vivo and In Vitro

10.21203/rs.3.rs-855996/v1 ◽

2021 ◽

Author(s):

Yun Ding ◽

Pengjie Tu ◽

Yiyong Chen ◽

Yangyun Huang ◽

Xiaojie Pan ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Response ◽

Reperfusion Injury ◽

Lung Tissue ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Tnf Α ◽

Anti Inflammatory

Abstract Background Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), which exert anti-inflammatory, anti-apoptotic, pro-proliferative, and antioxidant effects on the cardiovascular system. However, the role of CYP2J2 and EETs in pulmonary arterial hypertension (PAH) with lung ischemia-reperfusion injury (LIRI) remains unclear. In the present study, we investigated the effects of CYP2J2 overexpression and exogenous EETs on PAH with LIRI in vitro and in vivo.Methods CYP2J2 gene was transfected into rat lung tissue by recombinant adeno-associated virus (rAAV) to increase the levels of EETs in serum and lung tissue. A rat model of PAH with LIRI was constructed by tail vein injection of monocrotaline (50 mg/kg) for 4 weeks, followed by clamping of the left pulmonary hilum for 1 h and reperfusion for 2 h. In addition, we established a cellular model of human pulmonary artery endothelial cells (HPAECs) with TNF-α combined with hypoxic reoxygenation (anoxia for 8 h and reoxygenation for 16 h) to determine the effect and mechanism of exogenous EETs.Results CYP2J2 overexpression significantly reduced the inflammatory response, oxidative stress and apoptosis associated with lung injury in PAH with LIRI. In addition, exogenous EETs suppressed inflammatory response and reduced intracellular reactive oxygen species (ROS) production and inhibited apoptosis in a tumor necrosis factor alpha (TNF-α) combined hypoxia-reoxygenation model of HPAECs. Our further studies revealed that the anti-inflammatory effects of CYP2J2 overexpression and EETs might be mediated by PPARγ pathway; the anti-apoptotic effects might be mediated by the PI3K/Ak pathway.Conclusions CYP2J2 overexpression and EETs protect against PAH with LIRI via anti-inflammation, anti-oxidative stress and anti-apoptosis, suggesting that increased levels of EETs may be a promising strategy for the prevention and treatment of PAH with LIRI.

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