TNF-induced signaling mediates pleiotropic biological consequences including inflammation, immunity, cell proliferation and apoptosis. Misregulation of TNF signaling has been attributed as a major cause of chronic inflammatory diseases and cancer. Jumonji domain-containing protein 8 (JMJD8) belongs to the JmjC family. However, only part of the family members has been described as hydroxylase en...

Osteoarthritis (OA) is the most common form of arthritis, affecting an estimated 27 million Americans. The lack of current treatments to slow OA progression is due to the lack of both early detection methods and therapeutic targets for OA. Thus, there is an urgent need for the discovery of potential new therapeutic targets for the treatment of OA. Annexins are cytoplasmic proteins that, in the ...

The signaling of Toll-like receptors (TLRs) induces host defense against microbial invasion. Protein posttranslational modifications dynamically shape the strength and duration of the signaling pathways. It is intriguing to explore whether de-SUMOylation could modulate the TLR signaling. Here we identified SUMO-specific protease 6 (SENP6) as an intrinsic attenuator of the TLR-triggered inflamma...

β-Catenin is a central player in Wnt signaling, and activation of Wnt signaling is associated with cancer development. E-cadherin in complex with β-catenin mediates cell-cell adhesion, which suppresses β-catenin-dependent Wnt signaling. Recently, a tumor-suppressive role for E-cadherin has been reconsidered, as re-expression of E-cadherin was reported to enhance the metastatic potential of mali...

Susceptibility to mastitis is highest during the peripartal (transition) period and often concomitant with other comorbidities such as ketosis. Although infection pathogenic microorganisms immune-dysfunction around calving clearly play key roles in development, metabolic factors also contribute. Sirtuin 3 (SIRT3), a mitochondrial deacetylase regulating energy redox homeostasis, antagonizes lipo...

Asthma-related mortality has been decreasing due to inhaled corticosteroid use, but severe asthma remains a major clinical problem. One characteristic of severe asthma is resistance to steroid therapy, which is related to neutrophilic inflammation. Recently, the tumor necrosis factor superfamily member (TNFSF) 14/LIGHT has been recognized as a key mediator in severe asthmatic airway inflammatio...

Auto-reactive B lymphocytes and its abnormal CD40 signaling play important roles in the pathogenesis of systemic lupus erythematosus (SLE). In this study, we analyzed CD40 expression and CD40/CD154 induced activation of NF-κB signaling pathway in B cells from SLE patients. B cells from healthy volunteers and tonsilar B cells from chronic tonsillitis were used as negative and positive controls. ...

The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) represents a very aggressive human lymphoma entity. Constitutive NF-κB activation caused by chronic active B-cell receptor (BCR) signaling is common feature of many ABC DLBCL cells; however, the pathways linking BCR signaling to the NF-κB prosurvival network are largely unknown. Here we report that constitutive act...

Our previous study concerning brain trauma has shown that progesterone could regulate toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) signaling pathway in the brain, which also has been proved to play important roles in early brain injury (EBI) after subarachnoid hemorrhage (SAH). The aim of the current study was to investigate whether progesterone administration modulated TLR4/N...

Integrin-linked kinase (ILK) is a ubiquitously expressed and highly conserved serine-threonine protein kinase that regulates cellular responses to a wide variety of extracellular stimuli. ILK is involved in cell-matrix interactions, cytoskeletal organization, and cell signaling. ILK signaling has also been implicated in oncogenesis and progression of cancers. However, its role in the innate imm...