Heparan sulfate glycosaminoglycans (HS-GAGs) are not only the structural elements of tissue architecture but also regulate the bioavailability and transduction pathways of heparan sulfate-bound polypeptides released by cells or the extracellular matrix. Heparan sulfate-bound polypeptides include inflammatory mediators, chemokines, angiogenic factors, morphogens, and growth-promoting factors tha...

BACKGROUND It is well-documented that neonates can experience pain after injury. However, the contribution of individual populations of sensory neurons to neonatal pain is not clearly understood. Here we characterized the functional response properties and neurochemical phenotypes of single primary afferents after injection of carrageenan into the hairy hindpaw skin using a neonatal ex vivo rec...

BACKGROUND Leishmaniasis is a complex disease in which clinical outcome depends on factors such as parasite species, host genetics and immunity and vector species. In Brazil, Leishmania (Viannia) braziliensis is a major etiological agent of cutaneous (CL) and mucosal leishmaniasis (MCL), a disfiguring form of the disease, which occurs in ~10% of L. braziliensis-infected patients. Thus, clinical...

Inflammation in systemic sclerosis (SSc) is a prominent, but incompletely characterized feature in early stages of the disease. The goal of these studies was to determine the circulating levels, clinical correlates and biological effects of the acute phase protein serum amyloid A (SAA), a marker of inflammation, in patients with SSc. Circulating levels of SAA were determined by multiplex assays...

A subset of CC chemokines, acting through CC chemokine receptors (CCRs) 1 to 5, is instrumental in shaping inflammatory responses. Recently, we and others have demonstrated that the atypical chemokine receptor D6 actively sequesters and destroys many of these proinflammatory CC chemokines. This is critical for effective resolution of inflammation in vivo. Inflammation can be protumorigenic, and...

OBJECTIVE This study was designed to evaluate the histopathology of neuropathic ulcers and whether pressure relief could change such histological patterns. RESEARCH DESIGN AND METHODS We compared neuropathic plantar ulcers tissue excised from 10 diabetic patients (group A) with those taken from 10 patients with comparable lesions and glycemic control after 20 days in a total contact cast (gro...

The principal goal in treating surgical and non-surgical wounds, in particular for aged skin, is the need for rapid closure of the lesion. Cutaneous wound healing processes involve four phases including an inflammatory response with the induction of pro-inflammatory cytokines. If inflammation develops in response to bacterial infection, it can create a problem for wound closure. Reduced inflamm...

Patients with atopic dermatitis (AD) often suffer from food allergy and develop flares upon skin contact with food allergens. However, it is unclear whether T cells sensitized to allergens in the gut promote this skin inflammation. To address this question, we orally immunized WT mice and mice lacking the skin-homing chemokine receptor Ccr4 (Ccr4-/- mice) with OVA and then challenged them epicu...

The RAS signaling pathway is constitutively activated in psoriatic keratinocytes. We expressed activated H-RAS(V12G) in suprabasal keratinocytes of adult mice and observed rapid development of a psoriasis-like skin phenotype characterized by basal keratinocyte hyperproliferation, acanthosis, hyperkeratosis, intraepidermal neutrophil microabscesses, and increased T helper type 1 (Th1)/Th17 and T...

Neutrophilic dermatoses are a spectrum of autoinflammatory skin disorders that are characterized by extensive infiltration of neutrophils into the epidermis and dermis. The underlining biological pathways that are responsible for this heterogeneous group of cutaneous diseases have remained elusive. However, recent work from our laboratory and other groups has shown that missense mutations in Pt...