RAMP1 in Kupffer cells is a critical regulator in immune-mediated hepatitis

Inoue, Takuya; Yoshiya, Ikuto; Nishizawa, Nobuyuki; Eshima, Koji; Kojo, Ken; Otaka, Fumisato; Betto, Tomohiro; Yamane, Sakiko; Tsujikawa, Kazutake; Koizumi, Wasaburo; Murakami, Masataka

doi:10.1371/journal.pone.0200432

Cited by 14 publications

(9 citation statements)

References 30 publications

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“…RAMP1 signalling in immune cells attenuates inflammation in the skin and lung 30 . We also showed that CGRP interacts with immune cells to regulate inflammatory cytokines, which results in reducing chemical‐induced inflammation in the intestine 19 and liver 20 . In addition to its role in regulating inflammation, we showed that CGRP/RAMP1 signalling interacts with macrophages and fibroblasts to enhance angiogenic responses in mice with skin wounds, 24 peritonitis 26 and, as demonstrated in the present study, endometriosis.…”

Section: Discussionsupporting

confidence: 83%

“…30 We also showed that CGRP interacts with immune cells to regulate inflammatory cytokines, which results in reducing chemical-induced inflammation in the intestine 19 and liver. 20 In addition to its role in regulating inflammation, we showed that CGRP/RAMP1 signalling interacts with macrophages and fibroblasts to enhance angiogenic responses in mice with skin wounds, 24 peritonitis 26 and, as demonstrated in the present study, endometriosis. Accumulated fibroblasts in endometrial tissue implants appear to promote angiogenesis by inducing VEGF-A, 15,31 although in the present study cultured fibroblasts failed to up-regulate VEGF-A in response to CGRP, which is consistent with our previous findings.…”

Section: F I G U R Esupporting

confidence: 72%

“…10,16 Accumulated evidence indicates that the nervous system closely interacts with the immune system. For instance, the neuropeptide CGRP regulates immune functions, 10,17 acts on several kinds of immune cells, such as dendritic cells 18 and macrophages, 19,20 and down-regulates inflammation by inhibiting pro-inflammatory cytokines through RAMP1 signalling in immune cells. [18][19][20] Furthermore, we reported that the CGRP/RAMP1 axis in the nervous system regulates angiogenesis in tumour tissues 21 and in injured tissues caused by gastric ulcers 22 and ischaemia.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, the neuropeptide CGRP regulates immune functions, 10,17 acts on several kinds of immune cells, such as dendritic cells 18 and macrophages, 19,20 and down-regulates inflammation by inhibiting pro-inflammatory cytokines through RAMP1 signalling in immune cells. [18][19][20] Furthermore, we reported that the CGRP/RAMP1 axis in the nervous system regulates angiogenesis in tumour tissues 21 and in injured tissues caused by gastric ulcers 22 and ischaemia. 23 CGRP/RAMP1 also plays a role in lymphangiogenesis in mice with skin wounds 24 and with inflammation in the tail 25 and diaphragm.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of receptor activity–modifying protein 1 suppresses the development of endometriosis and the formation of blood and lymphatic vessels

Honda

Yoshiya

Hattori

et al. 2020

J Cellular Molecular Medi

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Section: Discussionsupporting

confidence: 83%

Section: F I G U R Esupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Inhibition of receptor activity–modifying protein 1 suppresses the development of endometriosis and the formation of blood and lymphatic vessels

Honda

Yoshiya

Hattori

et al. 2020

J Cellular Molecular Medi

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“…An effective method of isolating Kupffer cells was explored to eliminate endothelial cell contamination, which could be meaningful for illuminating Kupffer cell function and mechanism in diseases[22]. RAMP 1 in Kupffer cells mediates a crosstalk network involving infiltration of immune cells and pro-inflammatory cytokines secreted by Kupffer cells and splenic T cells, and such crosstalk network can regulate the immune response[23]. ATG5-dependent autophagy involved in crosstalk between Kupffer cells and cytokines (IL-6 and IL-10) mediated acute liver injury response[24].…”

Section: Cells Involved In Liver Fibrosismentioning

confidence: 99%

Crosstalk network among multiple inflammatory mediators in liver fibrosis

Zhangdi

Wang

et al. 2019

WJG

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Liver fibrosis is the common pathological basis of all chronic liver diseases, and is the necessary stage for the progression of chronic liver disease to cirrhosis. As one of pathogenic factors, inflammation plays a predominant role in liver fibrosis via communication and interaction between inflammatory cells, cytokines, and the related signaling pathways. Damaged hepatocytes induce an increase in pro-inflammatory factors, thereby inducing the development of inflammation. In addition, it has been reported that inflammatory response related signaling pathway is the main signal transduction pathway for the development of liver fibrosis. The crosstalk regulatory network leads to hepatic stellate cell activation and proinflammatory cytokine production, which in turn initiate the fibrotic response. Compared with the past, the research on the pathogenesis of liver fibrosis has been greatly developed. However, the liver fibrosis mechanism is complex and many pathways involved need to be further studied. This review mainly focuses on the crosstalk regulatory network among inflammatory cells, cytokines, and the related signaling pathways in the pathogenesis of chronic inflammatory liver diseases. Moreover, we also summarize the recent studies on the mechanisms underlying liver fibrosis and clinical efforts on the targeted therapies against the fibrotic response.

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Sensory Neurotransmitter Calcitonin Gene‐Related Peptide Modulates Tumor Growth and Lymphocyte Infiltration in Oral Squamous Cell Carcinoma

et al. 2022

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larynx, or hypopharynx. [2,3] Risk factors can be behavioral (i.e., tobacco and alcohol use) or infection-associated (i.e., human papillomavirus (HPV)), and these factors vary with geographic location. [4] Head and neck squamous cell carcinoma (SCC) constitutes 90% of cases of HNC and is associated with severe disease and high rates of recurrence despite advances in cancer treatment. [1] The oral cavity is innervated by cranial nerves with a high density of sensory nerves, originating mainly from the trigeminal ganglia (TG). [5] To date, histological patterns of cancer-nerve interaction, defined as perineural invasion (PNI), are identified as the presence of tumor cell clusters within the peripheral nerve sheath or infiltrating the nerves and/or tumor cells encircling one-third of the nerve circumference. [6] PNI was detected in up to 70% of oral SCC in the tongue and/ or floor of the mouth and has been demonstrated as an independent predictor of poor prognosis and an indicator of aggressive tumor behavior. [7][8][9][10] Prior research by Rahima et al. [11] and Laske et al. [12] found that PNI in early stage oral and oropharyngeal carcinomas has a highly negative association with recurrence-free survival and tumor differentiation. Systemic analysis of the neural influences within the cancer microenvironment, including identification of how PNI and other nerve-cancer interactions generally relate to poor prognosis, is crucial given that ongoing research is focusing on the neural invasion for targeted therapies of tumor regression. [13][14][15][16][17][18] Calcitonin gene-related peptide (CGRP) is the most abundant neurotransmitter in trigeminal ganglia neurons (TGN) innervating the tongue [19,20] and serves a prominent role in efferent signaling; upon activation of sensory nerve fibers, CGRP is released from peripheral nerve terminals and exerts paracrine effects on surrounding tissues [21] , including tumor cells. Two isoforms of CGRP exist; αCGRP, derived from the CALCA gene, is the principal form found in the central and peripheral nervous system, whereas βCGRP, derived from the CALCB gene, is found mainly in the enteric nervous system. [21] In a rat oral cancer model, a high percentage of αCGRPimmunoreactive nerve sprouting was found in the tumor microenvironment and orofacial sensitization was accompanied by upregulated αCGRP expression in the maxillary and

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RAMP1 in Kupffer cells is a critical regulator in immune-mediated hepatitis

Cited by 14 publications

References 30 publications

Inhibition of receptor activity–modifying protein 1 suppresses the development of endometriosis and the formation of blood and lymphatic vessels

Inhibition of receptor activity–modifying protein 1 suppresses the development of endometriosis and the formation of blood and lymphatic vessels

Crosstalk network among multiple inflammatory mediators in liver fibrosis

Sensory Neurotransmitter Calcitonin Gene‐Related Peptide Modulates Tumor Growth and Lymphocyte Infiltration in Oral Squamous Cell Carcinoma

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