CC Chemokine Family Members’ Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury—A Review of Clinical and Experimental Findings

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(7), P. 3788 - 3788

Published: March 28, 2024

Despite significant progress in modern medicine and pharmacology, damage to the nervous system with various etiologies still poses a challenge doctors scientists. Injuries lead neuroimmunological changes central (CNS), which may result both secondary development of tactile thermal hypersensitivity. In our review, based on analysis many experimental clinical studies, we indicate that mechanisms occurring at level brain after direct spinal cord peripheral nerve have common immunological basis. This suggests there are opportunities for similar pharmacological therapeutic interventions etiologies. Experimental data CNS/PNS damage, levels 16 among 28 CC-family chemokines, i.e., CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL17, CCL19, CCL20, CCL21, CCL22, increase and/or strong proinflammatory pronociceptive effects. According available literature data, further investigation is needed understanding role remaining especially six them were found humans but not mice/rats, CCL13, CCL14, CCL15, CCL16, CCL18, CCL23. Over past several years, results studies tools used indicated blocking individual receptors, e.g., CCR1 (J113863 BX513), CCR2 (RS504393, CCX872, INCB3344, AZ889), CCR3 (SB328437), CCR4 (C021 AZD-2098), CCR5 (maraviroc, AZD-5672, TAK-220), has beneficial effects CNS PNS. Recently, proved blockades exerted by double antagonists CCR1/3 (UCB 35625) CCR2/5 (cenicriviroc) very good anti-inflammatory antinociceptive addition, single (J113863, RS504393, SB328437, C021, maraviroc) dual chemokine receptor enhanced analgesic effect opioid drugs. review will display evidence multidirectional strategy modulation neuronal–glial–immune interactions can significantly improve health patients PNS changing activity chemokines belonging CC family. Moreover, case pain, combined administration such drugs could reduce doses minimize risk complications.

Language: Английский

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Mast cell–derived chymases are essential for the resolution of inflammatory pain in mice

Pain, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Abstract Immune cells play a critical role in the transition from acute to chronic pain. However, of mast pain remains underinvestigated. Here, we demonstrated that resolution inflammatory is markedly delayed cell–deficient mice. In response complete Freund adjuvant, mice showed greater levels nitric oxide, leukocyte infiltration, and altered cytokine/chemokine profile inflamed skin both sexes. wild-type mice, number cell cell–derived chymases, chymase 1 (CMA1) protease 4 (MCPT4), increased skin. Inhibiting enzymatic activity Consistently, local pharmacological administration recombinant CMA1 MCPT4 promoted hypersensitivity attenuated upregulation cytokines chemokines under inflammation. We identified CCL9 as target MCPT4. Inhibition recruitment CD206 + myeloid alleviated Our work reveals new chymases preventing suggests therapeutic avenues for treatment

Language: Английский

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A New Application for Cenicriviroc, a Dual CCR2/CCR5 Antagonist, in the Treatment of Painful Diabetic Neuropathy in a Mouse Model

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7410 - 7410

Published: July 5, 2024

The ligands of chemokine receptors 2 and 5 (CCR2 CCR5, respectively) are associated with the pathomechanism neuropathic pain development, but their role in painful diabetic neuropathy remains unclear. Therefore, aim our study was to examine function these factors hypersensitivity accompanying diabetes. Additionally, we analyzed analgesic effect cenicriviroc (CVC), a dual CCR2/CCR5 antagonist, its influence on effectiveness morphine. An increasing number experimental studies have shown that targeting more than one molecular target is advantageous compared coadministration individual pharmacophores terms effect. advantage using bifunctional compounds they gain simultaneous access two at same dose, positively affecting pharmacokinetics pharmacodynamics consequently leading improved analgesia. Experiments were performed male female Swiss albino mice streptozotocin (STZ, 200 mg/kg, i.p.) model neuropathy. We found blood glucose level increased, mechanical thermal developed 7th day after STZ administration. In mice, observed increased mRNA levels Ccl2, Ccl5, Ccl7, while additional increases Ccl8 Ccl12 levels. demonstrated for first time single administration relieves similar extent mice. Moreover, repeated morphine delays development opioid tolerance, best longest-lasting achieved by alone, which reduces STZ-exposed unlike morphine, no tolerance effects CVC until Day 15 treatment. Based results, suggest CCR2 CCR5 potent therapeutic option novel treatments patients.

Language: Английский

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Interaction between nasal epithelial cells and Tregs in allergic rhinitis responses to allergen via CCL1/CCR8

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 20, 2025

The airway epithelial barrier is the first defence against aeroallergens. Nasal cells (NECs) are vital in regulating innate and adaptive mucosal immunity allergic rhinitis (AR). Tregs produce cytokines essential for immunomodulatory activities allergen immunotherapy. Understanding relationship between NECs hyperresponsiveness network developing novel treatments. Using an vitro human Treg-NEC co-culture system of AR health control group, chemokine expression profiles were examined using immunohistochemistry, RT-PCR, ELISA, functional surface markers detected flow cytometric analysis. Correlation analysis was performed derived from CD4+CD8+Foxp3+ group after co-culture, including TSLP/CTLA4, CCL1/CTLA4, TSLP/CCR8, CCL1/CCR8. CCR8 CTLA-4 expressions co-culturing higher than single culture. Following Derp1 stimulation, TSLP, IL-25 TGF-β + increased. CCL1 mRNA lower group. In TSLP higher, protein levels decreased. There no significant differences IL-25, IL-10. When Treg added, changes similar to that observed pNECs. After CCL1/CCR8 positively correlated AR. Human pNECs can communicate with directly, may be pathway play a key role immune

Language: Английский

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Causal Relationship Between Circulating Inflammatory Cytokines and the Risk of Trigeminal Neuralgia: A Mendelian Randomization Study

Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(4)

Published: April 1, 2025

ABSTRACT Background Inflammatory regulators play a fundamental role in the development of trigeminal neuralgia (TN). However, precise mechanisms and causal relationship with risk TN remain poorly understood. Methods This study aimed to assess between 41 inflammatory cytokines using Mendelian randomization (MR) analysis. A two‐sample MR approach was utilized, employing genetic variation data on from large publicly available genome‐wide association (GWAS) comprising 1777 cases European ancestry 360,538 controls. Additionally, summary GWAS cytokines, 8293 healthy participants, were utilized. The exposure outcome primarily assessed inverse variance weighted (IVW) method, accompanied by sensitivity analyses. Results revealed an increased cutaneous T cell‐attracting chemokine（CTACK） (odds ratio [OR] = 1.187; 95% confidence interval [CI], 1.041–1.35; p 0.01) interferon (IFN)‐gamma（MIG） (OR 1.232; CI, 1.080–1.449; 0.01), while interleukin (IL)‐16 0.823; 0.685–0.989; 0.03) (IFN)‐G 0.779; 0.612–0.992; 0.04) associated decreased TN. Notably, no potential effect factors observed. Conclusion provides novel insights into pathogenesis TN, highlighting crucial risk. Significance advances our understanding identify roles specific cytokines. These results underscore importance inflammation suggest targets for new treatments.

Language: Английский

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Pharmacological modulation of neutrophils, in contrast to that of macrophages/microglia, is sex independent and delays the development of morphine tolerance in a mouse model of neuropathic pain

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 187, P. 118149 - 118149

Published: May 10, 2025

Language: Английский

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Mast cell-derived chymases are essential for the resolution of inflammatory pain in mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 7, 2024

Immune cells play a critical role in the transition from acute to chronic pain. However, of mast pain remains under-investigated. Here, we demonstrated that resolution inflammatory is markedly delayed mast-cell-deficient mice. In response Complete Freund Adjuvant (CFA), mice showed greater levels nitric oxide and altered cytokine/chemokine profile inflamed skin both sexes. Wild-Type (WT) mice, number cell cell-derived chymases; chymase 1 (CMA1) protease 4 (MCPT4) increased skin. Inhibiting enzymatic activity Consistently, local pharmacological administration recombinant CMA1 MCPT4 promoted hypersensitivity attenuated upregulation cytokines chemokines under inflammation. We identified CCL9 as target MCPT4. Inhibition recruitment CD206

Language: Английский

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TLR-4: a promising target for chemotherapy-induced peripheral neuropathy

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: Oct. 28, 2024

Language: Английский

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CCL2- and Notch2-mediated Central Sensitization in a Rat Chronic Pelvic Pain Model

In Vivo, Journal Year: 2023, Volume and Issue: 38(1), P. 205 - 212

Published: Dec. 25, 2023

Background/Aim: Chronic pelvic pain (CPP) is a common gynecological condition in women with multifactorial etiology. Some studies have revealed that patients CPP the same structural and functional changes matrix brain to other types of chronic pain. However, relationship between localized structure function central nervous system still unclear. Materials Methods: In this study, rat model was established by nerve ligation behavioral tests were used validate model. Afterwards, we compared expression CCL2 control rats observed their patterns blocking former group. addition, upregulated human microglia cells (HMC3) further observe effect on Notch2 pathway. Results: Our results showed chemokine ligand 2 (CCL2) serum exosomes, vascular endothelial cells, cerebrospinal fluid higher group than (p<0.05). HMC3 treated recombinant protein, significant increase mRNA protein observed. Conclusion: can activate signaling pathway plays an important role sensitization

Language: Английский

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Determining the link between psoriasis and Crohn's disease using bioinformatics and systems biology approaches

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: April 4, 2024

Psoriasis, like Crohn's Disease is a lasting inflammatory condition with complex mix of genetic and immune factors. It brings challenges to patients worldwide. This research delves into their connection by using RNA sequencing techniques gene expression analysis uncover pathways. emphasizes the significance NAMPT as influencing how they regulate responses disease development. The study sheds light on interplay among psoriasis merging datasets. provides perspectives, targeted treatment approaches. Improved diagnostic accuracy.

Language: Английский

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