Lack of Galanin 3 Receptor Aggravates Murine Autoimmune Arthritis

Botz, Bálint; Kemény, Ágnes; Brunner, Susanne M.; Locker, Felix; Csepregi, Janka Zsófia; Mócsai, Attila; Pintér, Erika; McDougall, Jason J.; Kofler, Barbara; Helyes, Zsuzsanna

doi:10.1007/s12031-016-0732-9

Cited by 15 publications

(16 citation statements)

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“…In agreement with its putative role in IBD, we reported anti-inflammatory effects of GAL 3 R signaling on neutrophil-related MPO levels in murine arthritis 13 . In contrast, pro-inflammatory properties of GAL 3 R signaling were observed in murine psoriasis 14 and pancreatitis 15 .…”

Section: Discussionsupporting

confidence: 85%

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Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model

Brunner

Reichmann

Leitner

et al. 2021

Sci Rep

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The regulatory (neuro)peptide galanin and its three receptors (GAL1–3R) are involved in immunity and inflammation. Galanin alleviated inflammatory bowel disease (IBD) in rats. However, studies on the galanin receptors involved are lacking. We aimed to determine galanin receptor expression in IBD patients and to evaluate if GAL2R and GAL3R contribute to murine colitis. Immunohistochemical analysis revealed that granulocytes in colon specimens of IBD patients (Crohn’s disease and ulcerative colitis) expressed GAL2R and GAL3R but not GAL1R. After colitis induction with 2% dextran sulfate sodium (DSS) for 7 days, mice lacking GAL3R (GAL3R-KO) lost more body weight, exhibited more severe colonic inflammation and aggravated histologic damage, with increased infiltration of neutrophils compared to wild-type animals. Loss of GAL3R resulted in higher local and systemic inflammatory cytokine/chemokine levels. Remarkably, colitis-associated changes to the intestinal microbiota, as assessed by quantitative culture-independent techniques, were most pronounced in GAL3R-KO mice, characterized by elevated numbers of enterobacteria and bifidobacteria. In contrast, GAL2R deletion did not influence the course of colitis. In conclusion, granulocyte GAL2R and GAL3R expression is related to IBD activity in humans, and DSS-induced colitis in mice is strongly affected by GAL3R loss. Consequently, GAL3R poses a novel therapeutic target for IBD.

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Section: Discussionsupporting

confidence: 85%

“…Accordingly, galanin potently modulates neutrophil, NK cell, monocyte and macrophage functions in vitro 8 – 11 . Furthermore, GAL 3 R is involved in inflammatory diseases in vivo, including experimental arthritis, psoriasis and pancreatitis 13 – 15 .…”

Section: Introductionmentioning

confidence: 99%

Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model

Brunner

Reichmann

Leitner

et al. 2021

Sci Rep

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“…Previous studies have demonstrated the importance of certain pro- and anti-inflammatory sensory neuropeptides in arthritis models [ 10 , 31 , 50 ], while the overall effect of sensory desensitization was found to be primarily anti-inflammatory and analgesic in our current study. The delayed decrease of MPO-activity has previously also been observed in the K/BxN serum transfer model, where mice deficient in PACAP, a major vasoactive peptide mediator, showed a similarly increased neutrophil ROS production in the late phase of arthritis [ 31 ].…”

Section: Discussionsupporting

confidence: 58%

Regulatory role of capsaicin-sensitive peptidergic sensory nerves in the proteoglycan-induced autoimmune arthritis model of the mouse

Horváth

Borbély

Bölcskei

et al. 2018

J Neuroinflammation

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ObjectiveThe regulatory role of capsaicin-sensitive peptidergic sensory nerves has been shown in acute inflammation, but little is known about their involvement in T/B-cell driven autoimmune arthritis. This study integratively characterized the function of these nerve endings in the proteoglycan-induced chronic arthritis (PGIA), a translational model of rheumatoid arthritis.MethodsPeptidergic afferents were defunctionalized by resiniferatoxin (RTX) pretreatment in BALB/c mice, PGIA was induced by repeated antigen challenges. Hind paw volume, arthritis severity, grasping ability and the mechanonociceptive threshold were monitored during the 17-week experiment. Myeloperoxidase activity, vascular leakage and bone turnover were evaluated by in vivo optical imaging. Bone morphology was assessed using micro-CT, the intertarsal small joints were processed for histopathological analysis.ResultsFollowing desensitization of the capsaicin-sensitive afferents, ankle edema, arthritis severity and mechanical hyperalgesia were markedly diminished. Myeloperoxidase activity was lower in the early, but increased in the late phase, whilst plasma leakage and bone turnover were not altered. Desensitized mice displayed similar bone spurs and erosions, but increased trabecular thickness of the tibia and bony ankylosis of the spine. Intertarsal cartilage thickness was not altered in the model, but desensitization increased this parameter in both the non-arthritic and arthritic groups.ConclusionThis is the first integrative in vivo functional and morphological characterization of the PGIA mouse model, wherein peptidergic afferents have an important regulatory function. Their overall effect is proinflammatory by increasing acute inflammation, immune cell activity and pain. Meanwhile, their activation decreases spinal ankylosis, arthritis-induced altered trabecularity, and cartilage thickness in small joints.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1364-5) contains supplementary material, which is available to authorized users.

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“…Therefore, it could be possible that GAL also induces tumor-suppressing functions in GAL 3 -R positive GAMs. Regarding immunity and inflammation, we reported recently that GAL 3 -R signaling has both pro-and anti-inflammatory properties (48,52).…”

Section: (Supplementarymentioning

confidence: 99%

Galanin System in Human Glioma and Pituitary Adenoma

et al. 2020

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Expression of neuropeptides and their corresponding receptors has been demonstrated in different cancer types, where they can play a role in tumor cell growth, invasion, and migration. Human galanin (GAL) is a 30-amino-acid regulatory neuropeptide which acts through three G protein-coupled receptors, GAL 1-R, GAL 2-R, and GAL 3-R that differ in their signal transduction pathways. GAL and galanin receptors (GALRs) are expressed by different tumors, and direct involvement of GAL in tumorigenesis has been shown. Despite its strong expression in the central nervous system (CNS), the role of GAL in CNS tumors has not been extensively studied. To date, GAL peptide expression, GAL receptor binding and mRNA expression have been reported in glioma, meningioma, and pituitary adenoma. However, data on the cellular distribution of GALRs are sparse. The aim of the present study was to examine the expression of GAL and GALRs in different brain tumors by immunohistochemistry. Anterior pituitary gland (n = 7), pituitary adenoma (n = 9) and glioma of different WHO grades I-IV (n = 55) were analyzed for the expression of GAL and the three GALRs with antibodies recently extensively validated for specificity. While high focal GAL immunoreactivity was detected in up to 40% of cells in the anterior pituitary gland samples, only one pituitary adenoma showed focal GAL expression, at a low level. In the anterior pituitary, GAL 1-R and GAL 3-R protein expression was observed in up to 15% of cells, whereas receptor expression was not detected in pituitary adenoma. In glioma, diffuse and focal GAL staining was noticed in the majority of cases. GAL 1-R was observed in eight out of nine glioma subtypes. GAL 2-R immunoreactivity was not detected in glioma and pituitary adenoma, while GAL 3-R expression was significantly associated to high-grade glioma (WHO grade IV). Most interestingly, expression of GAL and GALRs was observed in tumor-infiltrating immune cells, including neutrophils and glioma-associated macrophages/microglia. The presence of GALRs on tumor-associated immune cells, especially macrophages, indicates that GAL signaling contributes to homeostasis of the tumor microenvironment. Thus, our data indicate that GAL signaling in tumor-supportive myeloid cells could be a novel therapeutic target.

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Lack of Galanin 3 Receptor Aggravates Murine Autoimmune Arthritis

Cited by 15 publications

References 51 publications

Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model

Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model

Regulatory role of capsaicin-sensitive peptidergic sensory nerves in the proteoglycan-induced autoimmune arthritis model of the mouse

Galanin System in Human Glioma and Pituitary Adenoma

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