CCL2/CCR2 signaling elicits itch- and pain-like behavior in a murine model of allergic contact dermatitis

Jiang, Haowu; Wang, Tao; Shimada, Steven G.; Sun, Rui; Tan, ZC; Cui, Huan; LaMotte, Robert H.

doi:10.1016/j.bbi.2019.04.026

Cited by 48 publications

(36 citation statements)

References 53 publications

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“…Previous studies reported that CCR2 is present only in monocytes/macrophages and basophils, whereas Ccr2 mRNA is expressed in most leukocytes, including monocytes/ macrophages, T cells, B cells, natural killer cells, basophils, and dendritic cells [2]. However, CCR2 is constitutively expressed in neurons in murine brain, spinal cord, and dorsal root ganglia, and upregulation of CCL2 (the ligand of CCR2)-CCR2 axis in the disease state directly causes neuronal dysfunction through Akt signaling pathway [9][10][11]. Other studies reported that CCR2 is expressed in both infiltrating monocytes and microglia in a rodent model of traumatic brain injury [12].…”

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confidence: 99%

CCR2 is localized in microglia and neurons, as well as infiltrating monocytes, in the lumbar spinal cord of ALS mice

et al. 2020

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It remains controversial whether circulating monocytes expressing CCR2 infiltrate the central nervous system (CNS) and contribute to pathogenicity of amyotrophic lateral sclerosis (ALS). A previous report used conventional immunohistochemistry to show that CCR2 is exclusively expressed by astrocytes, but not infiltrating monocytes/ microglia or neurons, in the spinal cords of ALS model mice. In this study, we assessed the cellular distribution of CCR2 in the CNS of ALS mice using CCR2-reporter mice (Ccr2 rfp/+-Cx3cr1 gfp/+-SOD1 G93A Tg mice), a more sophisticated method for directly detecting the distribution of CCR2 protein. We found that infiltration of CCR2 + monocytes in the lumbar spinal cord increased over the course of disease progression. Moreover, from the middle stage of disease, CCR2 was partially distributed in microglia and neurons, but not astrocytes, in striking contrast to the previous findings. These novel observations suggested that CCR2 + monocyte infiltration leads to CNS environmental deterioration due to toxic conversion of microglia and neurons, creating a vicious cycle of neuroinflammation and leading to acceleration of ALS pathology. Our findings also show that this reporter mouse is a useful and powerful tool for obtaining new insights into the pathomechanisms of ALS.

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confidence: 99%

CCR2 is localized in microglia and neurons, as well as infiltrating monocytes, in the lumbar spinal cord of ALS mice

et al. 2020

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“…The murine model of ACD was constructed by applying the contact sensitizer squaric acid dibutylester (SADBE; Sigma, USA) referring to previous studies. 7 , 14 The abdomen of mice was shaved without any skin lesion on day 1 under the brief anesthesia with isoflurane (2% in oxygen). Later, “ACD” mice were sensitized with 25 µL of 1% SADBE in acetone solution superficially applied to shaved abdomen for three consecutive days (Days 2–4).…”

Section: Methodsmentioning

confidence: 99%

CXCL12/CXCR4 signaling induced itch and pain sensation in a murine model of allergic contact dermatitis

Liu

et al. 2020

Mol Pain

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Allergic contact dermatitis is a skin inflammatory disease manifested with itch and pain symptom around the inflamed area. Chemokines such as CXCL12 are involved in the pathophysiology of allergic contact dermatitis, but little has been known about the effect of CXCL12/CXCR4 signaling for nociceptive sensation accompanying allergic contact dermatitis. Our study showed that CXCL12 and CXCR4 were upregulated in trigeminal ganglion with the progression of allergic contact dermatitis through western blotting and immunofluorescence. CXCL12 and CXCR4 were mainly upregulated in small-diameter neurons, which were co-localized with nociceptive markers in trigeminal ganglion. CXCR4 and CXCL12 were also expressed in trigeminal ganglion neurons retrograded from the skin lesion. Intradermal injection of CXCL12 enhanced the itch- and pain-like behavior which could be relieved by AMD3100, a CXCR4 antagonist, without changes of mast cells. Our findings suggested that blockade of CXCL12/CXCR4 signaling pathway might be beneficial to relieve itch and pain sensation accompanying allergic contact dermatitis.

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“…Additionally, experimental evidence points towards the growing importance of certain itch-associated signaling pathways that may be targeted in the near future, including the spinal α2/α3 GABA A receptors, bovine adrenal medulla (BAM) 8-22 and the Mrgpr, sodium channels (Na V 1.7, Na V 1.8, Na V 1.9), natriuretic peptides (BNP) and their receptors (NPR-1), gastrin-releasing peptide receptor (GRPR), PAR2 and CCL2/CCR2 [232][233][234][235][236][237][238][239][240][241][242].…”

Section: Miscellaneous Modalitiesmentioning

confidence: 99%

Emerging Therapeutic Options for Chronic Pruritus

2020

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Chronic pruritus, defined as an unpleasant sensation resulting in a need to scratch that lasts more than 6 weeks, is a prevalent and bothersome symptom associated with both cutaneous and systemic conditions. Due to complex pathogenesis and profuse contributing factors, chronic pruritus therapy remains challenging. Regardless of the well-established antipruritic properties of classic pharmacotherapy (topical therapy, phototherapy and systemic therapy), these methods often provide insufficient relief for affected individuals. Owing to the growing interest in the field of pruritic research, further experimental and clinical data have emerged, continuously supporting the possibility of instigating novel therapeutic measures. This review covers the most relevant current modalities remaining under investigation that possess promising perspectives of approval in the near future, especially opioidergic drugs (mu-opioid antagonists and kappa-opioid agonists), neurokinin-1 receptor antagonists, biologic drugs, Janus kinase inhibitors, ileal bile acid transporter inhibitors, aryl hydrocarbon receptor agonists and histamine H 4 receptor antagonists.

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CCL2/CCR2 signaling elicits itch- and pain-like behavior in a murine model of allergic contact dermatitis

Cited by 48 publications

References 53 publications

CCR2 is localized in microglia and neurons, as well as infiltrating monocytes, in the lumbar spinal cord of ALS mice

CCR2 is localized in microglia and neurons, as well as infiltrating monocytes, in the lumbar spinal cord of ALS mice

CXCL12/CXCR4 signaling induced itch and pain sensation in a murine model of allergic contact dermatitis

Emerging Therapeutic Options for Chronic Pruritus

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