Bioactive compounds modulating Toll-like 4 receptor (TLR4)-mediated inflammation: pathways involved and future perspectives

Coutinho-Wolino, Karen Salve; Almeida, Patrícia Pereira; Mafra, Denise; Stockler‐Pinto, Milena Barcza

doi:10.1016/j.nutres.2022.09.001

Cited by 22 publications

(4 citation statements)

References 178 publications

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“…More studies are needed to elucidate the role of TLR4 in the different cell types, histological layers, or regions of the gastrointestinal tract, but taken together, these findings highlight the role of TLR4 in normal enteric nervous system function and emphasize its role as a therapeutic target [45,46]. Furthermore, TLR4 not only exerts an influence on the enteric nervous system, but also mediates the effects of gut microbiota and fine-tunes neuro-immune interactions in the whole organism.…”

Section: Discussionmentioning

confidence: 99%

Intestinal Region-Dependent Alterations of Toll-Like Receptor 4 Expression in Myenteric Neurons of Type 1 Diabetic Rats

et al. 2023

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Toll-like receptor 4 (TLR4) can activate pro-inflammatory cascades in the gastrointestinal tract. Our aim was to determine TLR4 expression in myenteric neurons of different gut regions using a type 1 diabetic model. Ten weeks after the onset of hyperglycemia, myenteric whole-mount preparations from the duodenum, ileum and colon of streptozotocin-induced diabetic, insulin-treated diabetic and control rats were prepared for TLR4/peripherin double-labelling fluorescent immunohistochemistry. Immunogold electron microscopy was applied to evaluate TLR4 expression in the myenteric perikaryon and neuropil. Tissue TLR4 levels were measured by enzyme-linked immunosorbent assay. In controls, the number and proportion of the TLR4-immunoreactive myenteric neurons showed an increasing tendency to aboral direction. These values were significantly higher in diabetics compared to controls in the duodenum and ileum, but were significantly lower in the colon. In diabetics, the distribution of TLR4-labelling gold particles between the perikaryon and neuropil of myenteric neurons varied in a different way by intestinal segment. TLR4 tissue concentration changed only in the diabetic duodenum, and it decreased in muscle/myenteric plexus-containing homogenates, while it increased in mucosa/submucosa/submucous plexus-containing samples relative to controls. Insulin had beneficial effects on TLR4 expression. These findings support that chronic hyperglycemia has segment-specific effects on TLR4 expression, contributing to gastrointestinal disorders in diabetic patients.

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Section: Discussionmentioning

confidence: 99%

Intestinal Region-Dependent Alterations of Toll-Like Receptor 4 Expression in Myenteric Neurons of Type 1 Diabetic Rats

et al. 2023

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“…On the contrary, the TRIF pathway does not seem to be affected by DS since LPS-induced expression of IL-10, a classical anti-inflammatory cytokine [ 62 ], and IFNγ mRNA are similar in DS-treated and CTRL horses. Studies in vivo on various animal models have highlighted that curcumin and even boswellic acids are able to reduce the expression of TLR4, MyD88, and NF-kB [ 66 , 67 ].…”

Section: Discussionmentioning

confidence: 99%

Dietary Supplementation with Boswellia serrata, Verbascum thapsus, and Curcuma longa in Show Jumping Horses: Effects on Serum Proteome, Antioxidant Status, and Anti-Inflammatory Gene Expression

Beghelli

Zallocco

Angeloni

et al. 2023

Life

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Intense exercise can cause inflammation and oxidative stress due to the production of reactive oxygen species. These pathophysiological processes are interdependent, and each one can induce the other, creating a vicious circle. A placebo-controlled blind study was carried out in show jumping horses (n. 16) to evaluate the effects of a commercial dietary supplement (Dolhorse® N.B.F. Lanes srl, Milan, Italy) containing Verbascum thapsus leaf powder (1.42%), Curcuma longa (14.280 mg/kg), and Boswellia serrata (Roxb ex Colebr) (14.280 mg/kg) extracts. Before and after 10 days of dietary supplementation, blood samples were collected to evaluate the protein levels, antioxidants, and inflammatory responses by proteomic analysis or real-time Reverse Transcriptase-Polymerase Chain Reaction (real-time RT-PCR). A total of 36 protein spots, connected to 29 proteins, were modulated by dietary supplementation, whereas real-time RT-PCR revealed a significant downregulation of proinflammatory cytokines (interleukin 1α (p < 0.05) and interleukin-6 (0.005), toll-like receptor 4 (p < 0.05), and IKBKB (p < 0.05) in supplemented sport horses. Immunoglobulin chains, gelsolin, plasminogen, vitamin D binding protein, apolipoprotein AIV, and filamin B were overexpressed, whereas haptoglobin, α-2-HS-glycoprotein, α2-macroglobulin, afamin, amine oxidase, 60S acidic ribosomal protein, and complement fragments 3, 4, and 7 were reduced. No effect was observed on the antioxidant defense systems. The present results suggest this phytotherapy may reinforce the innate immune responses, thus representing a valid adjuvant to alleviate inflammation, which is a pathophysiological process in sport horses.

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“…As a result, proinflammatory biomarkers are expressed, raising the risk of developing and progressing to the stage of noncommunicable disorders. 22 TLRs are important receptors in innate immunity. They identify particular ligands and activate signaling pathways downstream.…”

Section: •-mentioning

confidence: 99%

“…Additionally, Toll‐like receptor 4 (TLR4), one of the pattern‐recognizing receptors, activates some inflammatory pathway agonists, including nuclear factor‐B, interleukin‐1 receptor‐associated kinase 4 (IRAK4), and mitogen‐activated protein kinases (MAPKs) pathways. As a result, pro‐inflammatory biomarkers are expressed, raising the risk of developing and progressing to the stage of noncommunicable disorders 22 . TLRs are important receptors in innate immunity.…”

Section: Introductionmentioning

confidence: 99%

Role of TLR4 signaling pathway in the mitigation of damaged lung by low‐dose gamma irradiation

Fahmy,

Mohamed,

Mekkawy

et al. 2023

Cell Biochemistry & Function

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Organisms frequently suffer negative effects from large doses of ionizing radiation. However, radiation is not as hazardous at lower doses as was once believed. The current study aims to evaluate the possible radio‐adaptive effect induced by low‐dose radiation (LDR) in modulating high‐dose radiation (HDR) and N‐nitrosodiethylamine (NDEA)‐induced lung injury in male albino rats. Sixty‐four male rats were randomly divided into four groups: Group 1 (control): normal rats; Group 2 (D): rats given NDEA in drinking water; Group 3 (DR): rats administered with NDEA then exposed to fractionated HDR; and Group 4 (DRL): rats administered with NDEA then exposed to LDR + HDR. In the next stage, malondialdehyde (MDA), glutathione reduced (GSH), catalase (CAT), and superoxide dismutase (SOD) levels in the lung tissues were measured. Furthermore, the enzyme‐linked immunoassay analysis technique was performed to assess the Toll‐like receptor 4 (TLR4), interleukin‐1 receptor‐associated kinase 4 (IRAK4), and mitogen‐activated protein kinases (MAPK) expression levels. Histopathological and DNA fragmentation analyses in lung tissue, in addition to hematological and apoptosis analyses of the blood samples, were also conducted. Results demonstrated a significant increase in antioxidant defense and a reduction in MDA levels were observed in LDR‐treated animals compared to the D and DR groups. Additionally, exposure to LDR decreased TLR4, IRAK4, and MAPK levels, decreased apoptosis, and restored all the alterations in the histopathological, hematological parameters, and DNA fragmentation, indicating its protective effects on the lung when compared with untreated rats. Taken together, LDR shows protective action against the negative effects of subsequent HDR and NDEA. This impact may be attributable to the adaptive response induced by LDR, which decreases DNA damage in lung tissue and activates the antioxidative, antiapoptotic, and anti‐inflammatory systems in the affected animals, enabling them to withstand the following HDR exposure.

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Bioactive compounds modulating Toll-like 4 receptor (TLR4)-mediated inflammation: pathways involved and future perspectives

Cited by 22 publications

References 178 publications

Intestinal Region-Dependent Alterations of Toll-Like Receptor 4 Expression in Myenteric Neurons of Type 1 Diabetic Rats

Intestinal Region-Dependent Alterations of Toll-Like Receptor 4 Expression in Myenteric Neurons of Type 1 Diabetic Rats

Dietary Supplementation with Boswellia serrata, Verbascum thapsus, and Curcuma longa in Show Jumping Horses: Effects on Serum Proteome, Antioxidant Status, and Anti-Inflammatory Gene Expression

Role of TLR4 signaling pathway in the mitigation of damaged lung by low‐dose gamma irradiation

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