The story of clobenpropit and CXCR4: can be an effective drug in cancer and autoimmune diseases? DOI Creative Commons
Mitra Abbasifard, Kowsar Bagherzadeh, Hossein Khorramdelazad

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 12, 2024

Clobenpropit is a histamine H3 receptor antagonist and has developed as potential therapeutic drug due to its ability inhibit CXCR4, chemokine involved in autoimmune diseases cancer pathogenesis. The CXCL12/CXCR4 axis involves several biological phenomena, including cell proliferation, migration, angiogenesis, inflammation, metastasis. Accordingly, inhibiting CXCR4 can have promising clinical outcomes patients with malignancy or disorders. Based on available knowledge, effectively regulate the release of monocyte-derived inflammatory cytokine such juvenile idiopathic arthritis (JIA), presenting targeted target possible advantages over current approaches. This review summarizes intricate interplay between molecular mechanisms underlying their interactions, comprehensively analyzing impact immune regulation. Furthermore, we discuss preclinical investigations highlighting probable efficacy for managing cancer. Through this study, aim clarify immunomodulatory role disadvantages novel opportunity.

Language: Английский

The toll like receptor 7 pathway and the sex bias of systemic lupus erythematosus DOI Creative Commons

R. Hal Scofield,

Jonathan D. Wren, Valerie M. Lewis

et al.

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

Published: Feb. 20, 2025

Systemic lupus erythematosus (SLE) predominately affects women with a ratio of females-to-males about 9:1. The complement sex chromosomes may play and important role in the mechanism bias. Previous work has shown that men Klinefleter's syndrome (47,XXY) as well 47,XXX are found excess among SLE patients Sjogren's disease, systemic sclerosis idiopathic inflammatory myositis. cells more than one X chromosome, all but is inactivated. However, chromosome inactivation, mediated by long noncoding RNA X-inactive specific transcript, or XIST, not complete approximately 10% genes non-recombining region escaping inactivation. In TLR7 signaling pathway, both TLR adaptor interacting endolysosomal SLC15A4 (TASL) escape Comparing male female immune cells, there increased related to expression these chromosome. Cells also express while do not. source ligand for TLR7, been increase signaling. Thus, we propose mechanisms operating act mutual way mediate an dose effect bias autoimmune disease.

Language: Английский

Citations

2
Role of Glial Cells and Receptors in Schizophrenia Pathogenesis DOI
Yousef Tizabi, Marta C. Antonelli,

Daniela Tizabi

et al.

Neurochemical Research, Journal Year: 2025, Volume and Issue: 50(2)

Published: Jan. 27, 2025

Language: Английский

Citations

0
A novel TIRAP-MyD88 inhibitor blocks TLR7- and TLR8-induced type I IFN responses DOI Creative Commons
Kaja Elisabeth Nilsen, Jørgen Stenvik, Astrid Skjesol

et al.

Published: April 28, 2025

Abstract Endosomal toll-like receptors TLR7 and TLR8 are critical sensors of microbial RNA that initiate antiviral antibacterial immune responses through type I interferon (IFN) proinflammatory cytokine production. While TIRAP is traditionally associated with plasma membrane TLR signaling, recent evidence suggests it also contributes to signaling via endosomal TLRs. Here, we examined the role in TLR7/8 using P7-Pen, a novel SLAMF1-derived peptide disrupts TIRAP–MyD88 interaction. In primary human monocytes whole blood model, P7-Pen inhibited TLR7- TLR8-induced expression secretion IRF5-regulated cytokines IFNβ, IL-12p40, IL-12p70, without effect on TNF or IL-6. Mechanistically, blocked recruitment TLR8-MyD88 complex, leading reduced late-stage IRAK1 activation, Akt IKKα/β phosphorylation, downstream IRF5 dimerization nuclear translocation. Inhibition Staphylococcus aureus -induced production by was bacterial phagocytosis, impairing delivery RNA. Notably, failed inhibit murine responses, which correlated lack MyD88 mouse macrophages following ligand stimulation, highlighting species-specific differences mechanisms. These findings support noncanonical for regulating IRF5-dependent TLR8, demonstrate selective disruption effectively attenuates IFNβ This strategy may hold therapeutic potential diseases characterized dysregulated IFN such as systemic lupus erythematosus chronic infections.

Language: Английский

Citations

0
X inactivation shows frail ends when mice age DOI
Anton Wutz

Nature Aging, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

Citations

0
Pharmacological Mechanism of Chinese Medicine in Systemic Lupus Erythematosus: A Narrative Review DOI

Boyu Zhu,

Zhichao Liu,

Zhen-Xi Zhao

et al.

Chinese Journal of Integrative Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 5, 2024

Language: Английский

Citations

1
Immune Mechanisms and Biomarkers in Systemic Lupus Erythematosus DOI Open Access
Ioannis Parodis, Christopher Sjöwall

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9965 - 9965

Published: Sept. 15, 2024

The immense heterogeneity of the chronic, inflammatory, autoimmune disease systemic lupus erythematosus (SLE), both with regard to immunological aberrancies and clinical manifestations, poses diagnostic difficulties challenges in management patients [...]

Language: Английский

Citations

1
An exploration of the natural and acquired immunological mechanisms to high-risk human papillomavirus infection and unmasking immune escape in cervical cancer: A concise synopsis DOI Creative Commons

Mohammed Mohsen Mohammed,

Zaytoon A. Al-Khafaji,

Nadia Mudher Al-Hilli

et al.

Tzu Chi Medical Journal, Journal Year: 2024, Volume and Issue: 37(1), P. 28 - 41

Published: Dec. 3, 2024

The most common STD that triggers cervical cancer is the human papillomavirus. More than 20 types of papillomavirus (HPV) can induce uterine cancer. Almost all women acquire genital HPV infection soon after their first intercourse, with them clearing virus within 3 years. An immune response necessary to clear. responders are innate system elements composed macrophages, keratinocytes, natural killer cells, and T-lymphocytic (NKT) cells. Cytotoxic T lymphocytes (CTLs) comprise second line defense kill HPV16-infected cells expressing various peptides derived from transforming early viral oncoproteins, mainly E2•E6. Even though manage trick away our systems, all, it important emphasize replication does not host It replicate antigens or cause inflammation. HPV16 E6 E7 genes suppress cell type 1 interferons (IFNs), which detectable infection. patient may have immunological tolerance; hence, there no costimulatory signals inflammatory cytokines like IFNs during antigen recognition. Evidence shows HlA class I generations been inhibited by E5, could protect this tumor CTL attack. responsible for initiating immunotolerance increasing regulatory (Treg) repress regression. Evasion protection plays a critical role in outcome persistent development Vaccination against 18 adolescence effective method preventing women, considering processes involved.

Language: Английский

Citations

1
The story of clobenpropit and CXCR4: can be an effective drug in cancer and autoimmune diseases? DOI Creative Commons
Mitra Abbasifard, Kowsar Bagherzadeh, Hossein Khorramdelazad

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 12, 2024

Clobenpropit is a histamine H3 receptor antagonist and has developed as potential therapeutic drug due to its ability inhibit CXCR4, chemokine involved in autoimmune diseases cancer pathogenesis. The CXCL12/CXCR4 axis involves several biological phenomena, including cell proliferation, migration, angiogenesis, inflammation, metastasis. Accordingly, inhibiting CXCR4 can have promising clinical outcomes patients with malignancy or disorders. Based on available knowledge, effectively regulate the release of monocyte-derived inflammatory cytokine such juvenile idiopathic arthritis (JIA), presenting targeted target possible advantages over current approaches. This review summarizes intricate interplay between molecular mechanisms underlying their interactions, comprehensively analyzing impact immune regulation. Furthermore, we discuss preclinical investigations highlighting probable efficacy for managing cancer. Through this study, aim clarify immunomodulatory role disadvantages novel opportunity.

Language: Английский

Citations

0