Human GBP1 facilitates the rupture of the containing vacuole and inflammasome activation.

Inflammasomes are essential for host defense against intracellular bacterial pathogens like , as they activate caspases, which promote cytokine release and cell death to control infection. In mice, interferon (IFN) signaling promotes inflammasome responses against bacteria by inducing a family of IFN-inducible GTPases known as guanylate-binding proteins (GBPs). Within murine macrophages, IFN promotes the rupture of the -containing vacuole (LCV), while GBPs are dispensable for this process.

Highly selective inhibition of Bruton's tyrosine kinase attenuates skin and brain disease in murine lupus.

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects different end organs, including skin and brain. We and others have previously shown the importance of macrophages in the pathogenesis of cutaneous and neuropsychiatric lupus. Additionally, autoantibodies produced by autoreactive B cells are thought to play a role in both the skin and central nervous system pathologies associated with SLE.

Neutrophils and Ly6Chi monocytes collaborate in generating an optimal cytokine response that protects against pulmonary Legionella pneumophila infection.

Early responses mounted by both tissue-resident and recruited innate immune cells are essential for host defense against bacterial pathogens. In particular, both neutrophils and Ly6Chi monocytes are rapidly recruited to sites of infection. While neutrophils and monocytes produce bactericidal molecules, such as reactive nitrogen and oxygen species, both cell types are also capable of synthesizing overlapping sets of cytokines important for host defense.

TWEAK is not elevated in patients with newly diagnosed inflammatory bowel disease.

Objective: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) may be involved in the pathogenesis of inflammatory bowel disease. The aim was to investigate if TWEAK may reflect disease activity in inflammatory bowel disease.

Materials And Methods: In this cohort study, 139 consecutive patients with newly diagnosed and previously untreated inflammatory bowel disease - 95 with ulcerative colitis (UC) and 44 with Crohn's disease (CD) - underwent colonoscopy.

CSF-1R inhibition attenuates renal and neuropsychiatric disease in murine lupus.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that can affect multiple end organs. Kidney and brain are two of the organs most commonly involved in SLE. Past studies have suggested the importance of macrophages in the pathogenesis of lupus nephritis (LN).

Fn14 deficiency protects lupus-prone mice from histological lupus erythematosus-like skin inflammation induced by ultraviolet light.

The cytokine TNF-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 are involved in cell survival and cytokine production. The TWEAK/Fn14 pathway plays a role in the pathogenesis of spontaneous cutaneous lesions in the MRL/lpr lupus strain; however, the role of TWEAK/Fn14 in disease induced by ultraviolet B (UVB) irradiation has not been explored. MRL/lpr Fn14 knockout (KO) was compared to MRL/lpr Fn14 wild-type (WT) mice following exposure to UVB.

B cell and/or autoantibody deficiency do not prevent neuropsychiatric disease in murine systemic lupus erythematosus.

Background: Neuropsychiatric lupus (NPSLE) can be one of the earliest clinical manifestations in human lupus. However, its mechanisms are not fully understood. In lupus, a compromised blood-brain barrier may allow for the passage of circulating autoantibodies into the brain, where they can induce neuropsychiatric abnormalities including depression-like behavior and cognitive abnormalities.

Intracerebroventricular administration of TNF-like weak inducer of apoptosis induces depression-like behavior and cognitive dysfunction in non-autoimmune mice.

Fn14, the sole known signaling receptor for the TNF family member TWEAK, is inducibly expressed in the central nervous system (CNS) in endothelial cells, astrocytes, microglia, and neurons. There is increasing recognition of the importance of the TWEAK/Fn14 pathway in autoimmune neurologic conditions, including experimental autoimmune encephalomyelitis and neuropsychiatric lupus. Previously, we had found that Fn14 knockout lupus-prone MRL/lpr mice display significantly attenuated neuropsychiatric manifestations.

Neuropsychiatric systemic lupus erythematosus persists despite attenuation of systemic disease in MRL/lpr mice.

Background: Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease marked by both B and T cell hyperactivity which commonly affects the joints, skin, kidneys, and brain. Neuropsychiatric disease affects about 40 % of SLE patients, most frequently manifesting as depression, memory deficits, and general cognitive decline. One important and yet unresolved question is whether neuropsychiatric SLE (NPSLE) is a complication of systemic autoimmunity or whether it is primarily driven by brain-intrinsic factors.

Characterization and assessment of nanoencapsulated sanguinarine chloride as a potential treatment for melanoma.

Sanguinarine has a history of use in both folk medicine and early dermatology for the treatment of cutaneous neoplasms. Applied indiscriminately, bloodroot is an escharotic agent with potential to cause extensive tissue necrosis. However, when used in a controlled fashion, sanguinarine imparts selective cytotoxic/anti-proliferative activity through multiple mechanisms against human/ murine melanoma.

TNF-like weak inducer of apoptosis promotes blood brain barrier disruption and increases neuronal cell death in MRL/lpr mice.

Neuropsychiatric disease is one of the most common manifestations of human systemic lupus erythematosus, but the mechanisms remain poorly understood. In human brain microvascular endothelial cells in vitro, TNF-like weak inducer of apoptosis (TWEAK) decreases tight junction ZO-1 expression and increases the permeability of monolayer cell cultures. Furthermore, knockout (KO) of the TWEAK receptor, Fn14, in the MRL/lpr lupus mouse strain markedly attenuates neuropsychiatric disease, as demonstrated by significant reductions in depressive-like behavior and improved cognitive function.

TWEAK/Fn14 Signaling Involvement in the Pathogenesis of Cutaneous Disease in the MRL/lpr Model of Spontaneous Lupus.

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK, TNFSF12) and its sole receptor Fn14, belonging to the TNF ligand and receptor superfamilies respectively, are involved in cell survival and cytokine production. The role of TWEAK/Fn14 interactions in the pathogenesis of cutaneous lupus has not been explored. TWEAK treatment of murine PAM212 keratinocytes stimulated the secretion of RANTES via Fn14 and promoted apoptosis.

Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent.

Burn wounds are often complicated by bacterial infection, contributing to morbidity and mortality. Agents commonly used to treat burn wound infection are limited by toxicity, incomplete microbial coverage, inadequate penetration, and rising resistance. Curcumin is a naturally derived substance with innate antimicrobial and wound healing properties.

T cells targeting a neuronal paraneoplastic antigen mediate tumor rejection and trigger CNS autoimmunity with humoral activation.

Paraneoplastic neurologic diseases (PND) involving immune responses directed toward intracellular antigens are poorly understood. Here, we examine immunity to the PND antigen Nova2, which is expressed exclusively in central nervous system (CNS) neurons. We hypothesized that ectopic expression of neuronal antigen in the periphery could incite PND.