Immunopharmacology and immunotoxicology · 2026
Protective effects of histamine H4 receptor antagonist on the inflammatory responses in B cells in a mouse model of multiple sclerosis.
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Al-Mazroua Haneen A, Alhamami Hussain N, Nadeem Ahmed, Ansari Mushtaq A, Bakheet Saleh A, Attia Sabry M, Sarawi Wedad S, Alomar Hatun A, Alsaad Abdulaziz M S, Alshamrani Ali A, Ahmad Sheikh F
Аннотация
BACKGROUND: Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) driven by autoimmune mechanisms. However, growing evidence indicates that B lymphocytes may contribute to the disease through antigen presentation and the production of proinflammatory mediators. This study aimed to examine the effect of JNJ 10191584 (JNJ), a potent and selective H4R antagonist, on EAE progression and to uncover the underlying mechanisms.
METHODS: The research explored the potential impact of H4R antagonists on inflammatory responses in B cells within an EAE mouse model of MS. EAE mice received an oral dose of JNJ at 6 mg/kg daily, starting on day 10 and continuing until day 42. Flow cytometry assessed JNJ's effect on the expression of NF-κB p65, IκBα, Notch1, Notch3, IL-2, IL-6, GM-CSF, iNOS, TNF-α, and MCP-1 in CD19+ B cells. We used RT-PCR to assess the impact of JNJ on mRNA levels of these inflammatory markers in brain tissue.
RESULTS: In EAE mice, JNJ treatment reduced the number of CD19+ cells expressing NF-κB p65, IκBα, Notch1, Notch3, IL-2, IL-6, GM-CSF, iNOS, and MCP-1. Additionally, JNJ decreased mRNA expression of inflammatory markers in brain tissue compared with vehicle-treated mice.
CONCLUSIONS: These results suggest that targeting H4R with antagonists could offer a new therapeutic approach for MS by specifically modulating B-cell-mediated inflammation.
METHODS: The research explored the potential impact of H4R antagonists on inflammatory responses in B cells within an EAE mouse model of MS. EAE mice received an oral dose of JNJ at 6 mg/kg daily, starting on day 10 and continuing until day 42. Flow cytometry assessed JNJ's effect on the expression of NF-κB p65, IκBα, Notch1, Notch3, IL-2, IL-6, GM-CSF, iNOS, TNF-α, and MCP-1 in CD19+ B cells. We used RT-PCR to assess the impact of JNJ on mRNA levels of these inflammatory markers in brain tissue.
RESULTS: In EAE mice, JNJ treatment reduced the number of CD19+ cells expressing NF-κB p65, IκBα, Notch1, Notch3, IL-2, IL-6, GM-CSF, iNOS, and MCP-1. Additionally, JNJ decreased mRNA expression of inflammatory markers in brain tissue compared with vehicle-treated mice.
CONCLUSIONS: These results suggest that targeting H4R with antagonists could offer a new therapeutic approach for MS by specifically modulating B-cell-mediated inflammation.