Role of Interleukin-1 Family Members and Signaling Pathways in KSHV Pathogenesis

Interleukin-1 (IL-1) family and Kupffer cells are linked with liver regeneration, but their precise roles remain unclear. IL-1 family members are pleiotropic factors with a range of biological roles in liver diseases, inducing hepatitis, cirrhosis, and hepatocellular carcinoma, as well as liver regeneration. Kupffer cells are the main source of IL-1 and IL-1 receptor antagonist (IL-1Ra), the key members of IL-1 family. This systemic review highlights a close association of IL-1 family members and Kupffer cells with liver regeneration, although their specific roles are inconclusive. Moreover, IL-1 members are proposed to induce effects on liver regeneration through Kupffer cells.

Download Full-text

Inhibitory Role of an Aeromonas hydrophila TIR Domain Effector in Antibacterial Immunity by Targeting TLR Signaling Complexes in Zebrafish

Frontiers in Microbiology ◽

10.3389/fmicb.2021.694081 ◽

2021 ◽

Vol 12 ◽

Author(s):

Huai-ping Tang ◽

Chen Huang ◽

Chong-bin Hu ◽

Hao Li ◽

Tong Shao ◽

...

Keyword(s):

Signaling Pathways ◽

Aeromonas Hydrophila ◽

Protein Complexes ◽

Interleukin 1 ◽

Tumor Necrosis Factor Receptor ◽

Therapeutic Interventions ◽

Death Domain ◽

Tir Domain ◽

Myeloid Differentiation Factor

The Toll/interleukin-1 receptor (TIR) domain is a structural unit responsible for the assembly of signal protein complexes in Toll-like receptor (TLR) and interleukin-1 receptor signaling pathways. TIR domain homologs are found in a considerable number of bacteria and enhance bacterial infection and survival in host organisms. However, whether TIR domain homologs exist in Aeromonas hydrophila, a ubiquitous waterborne bacterium in aquatic environments, remains poorly understood. In this study, a TIR domain protein (TcpAh) was identified from A. hydrophila JBN2301. TIR domain of TcpAh is highly homologous to the counterpart domains in TLRs and myeloid differentiation factor 88 (MyD88). The zebrafish infected with mutant A. hydrophila with tcpAh deletion had a remarkably lower mortality than those infected with the wild-type strain. This result suggests that TcpAh is a crucial virulence factor for A. hydrophila infection. TcpAh exhibited a strong ability to associate with MyD88, tumor necrosis factor receptor-associated factor 3 (TRAF3) and TRAF-associated NF-κB activator-binding kinase 1 (TBK1) in TIR–TIR, TIR–Death domain (DD), and other alternative interactions. This finding suggests that TcpAh extensively interferes with MyD88 and TIR domain-containing adapter inducing interferon (IFN)-β (TRIF) signaling pathways downstream of TLRs. Consequently, CD80/86 expression was suppressed by TcpAh via attenuating TLR-stimulated NF-κB activation, which ultimately led to the impairment of the major costimulatory signal essential for the initiation of adaptive humoral immunity against A. hydrophila infection. We believe that this study is the first to show a previously unrecognized mechanism underlying A. hydrophila evades from host antibacterial defense by intervening CD80/86 signal, which bridges innate and adaptive immunity. The mechanism will benefit the development of therapeutic interventions for A. hydrophila infection and septicemia by targeting TcpAh homologs.

Download Full-text

Role of signaling pathway in biological cause of Rheumatoid arthritis

Current Drug Research Reviews ◽

10.2174/2589977512999201109215004 ◽

2020 ◽

Vol 12 ◽

Author(s):

Rakesh Kumar Chauhan ◽

Pramod Kumar Sharma ◽

Shikha Srivastava

Keyword(s):

Rheumatoid Arthritis ◽

Protein Kinase ◽

Signaling Pathways ◽

Interleukin 1 ◽

Development Stage ◽

The Body ◽

Mitogen Activated Protein Kinase ◽

Mitogen Activated Protein ◽

Heart Blood

Abstract:: Rheumatoid Arthritis is a chronic progressive inflammatory auto-immune disease in which the immune system of the body attacks its cartilage and joints lining. It not only affects synovial joints but also many other sites including heart, blood vessels, and skins. It is more common in females than in males. The exact cause of rheumatoid arthritis is not well established but the hypothesis reported in the literature is that in the development stage of the disease, both genetics and environmental factors can play an inciting role. Along with these factors alteration in the normal physiology of enzymatic action, acts as a trigger to develop this condition. Numerous signaling pathways involved in the pathogenesis of Rheumatoid Arthritis involves activation of mitogen-activated protein kinase, kinases Janus family, P-38 Mitogen-Activated Protein Kinase, Nuclear Factor-kappa B. Interleukin-1 to play a proinflammatory cytokine that plays an important role in inflammation in RA. These are also associated with an increase in neutrophil, macrophage and lymphocytic chemotaxis, mast cell degranulation, activation, maturation and survival of T-cells and B-cells activated. These signaling pathways also show that p38α downregulation in myeloid cells exacerbates the severity of symptoms of arthritis. Thus, present review carters about the detail of different signaling pathways and their role in rheumatoid arthritis.

Download Full-text

The nuclear receptor 4A family members: mediators in human disease and autophagy

Cellular & Molecular Biology Letters ◽

10.1186/s11658-020-00241-w ◽

2020 ◽

Vol 25 (1) ◽

Author(s):

Liqun Chen ◽

Fengtian Fan ◽

Lingjuan Wu ◽

Yiyi Zhao

Keyword(s):

Drug Development ◽

Signaling Pathways ◽

Nuclear Receptor ◽

Human Disease ◽

Family Members ◽

Current Understanding ◽

Human Diseases ◽

Disease Therapy ◽

Development Processes

Abstract The Nuclear receptor 4A (NR4A) subfamily, which belongs to the nuclear receptor (NR) superfamily, has three members: NR4A1 (Nur77), NR4A2 (Nurr1) and NR4A3 (Nor1). They are gene regulators with broad involvement in various signaling pathways and human disease responses, including autophagy. Here, we provide a concise overview of the current understanding of the role of the NR4A subfamily members in human diseases and review the research into their regulation of cell autophagy. A deeper understanding of these mechanisms has potential to improve drug development processes and disease therapy.

Download Full-text

The role of interleukin-1 family members in hyperuricemia and gout

Joint Bone Spine ◽

10.1016/j.jbspin.2020.105092 ◽

2020 ◽

pp. 105092

Author(s):

Viola Klück ◽

Ruiqi Liu ◽

Leo A B Joosten

Keyword(s):

Interleukin 1 ◽

Family Members

Download Full-text

Research Advances in the Role of the Poly ADP Ribose Polymerase Family in Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.790967 ◽

2021 ◽

Vol 11 ◽

Author(s):

Huanhuan Sha ◽

Yujie Gan ◽

Renrui Zou ◽

Jianzhong Wu ◽

Jifeng Feng

Keyword(s):

Signaling Pathways ◽

Clinical Application ◽

Molecular Basis ◽

Rapid Development ◽

Family Members ◽

Genomic Stability ◽

Regulatory Mechanisms ◽

Breast Cancers ◽

The Future

Poly ADP ribose polymerases (PARPs) catalyze the modification of acceptor proteins, DNA, or RNA with ADP-ribose, which plays an important role in maintaining genomic stability and regulating signaling pathways. The rapid development of PARP1/2 inhibitors for the treatment of ovarian and breast cancers has advanced research on other PARP family members for the treatment of cancer. This paper reviews the role of PARP family members (except PARP1/2 and tankyrases) in cancer and the underlying regulatory mechanisms, which will establish a molecular basis for the clinical application of PARPs in the future.

Download Full-text