Lack of Endogenous Annexin A1 Increases Mast Cell Activation and Exacerbates Experimental Atopic Dermatitis.

Annexin A1 (AnxA1) is a protein with potent anti-inflammatory actions and an interesting target that has been poorly explored in skin inflammation. This work evaluated the lack of endogenous AnxA1 in the progression of ovalbumin (OVA)-induced atopic dermatitis (AD)-like skin lesions. OVA/Alum-immunized C57BL/6 male wild-type (WT) and AnxA1 null (AnxA1-/-) mice were challenged with drops containing OVA on days 11, 14⁻18 and 21⁻24. The AnxA1-/- AD group exhibited skin with intense erythema, erosion and dryness associated with increased skin thickness compared to the AD WT group. The lack of endogenous AnxA1 also increased IgE relative to WT animals, demonstrating exacerbation of the allergic response. Histological analysis revealed intense eosinophilia and mast-cell activation in AD animals, especially in AnxA1-/-. Both AD groups increased skin interleukin (IL)-13 levels, while IL-17A was upregulated in AnxA1-/- lymph nodes and mast cells. High levels of phosphorylated ERK were detected in keratinocytes from AD groups. However, phospho-ERK levels were higher in the AnxA1-/- when compared to the respective control groups. Our results suggest AnxA1 as an important therapeutic target for inflammatory skin diseases.

Galectin-3: role in ocular allergy and potential as a predictive biomarker.

AIMS: To evaluate galectin-3 (Gal-3), a ß-galactoside binding protein, as a possible biomarker in ocular allergy and further investigated the role of endogenous Gal-3 in a murine model of ovalbumin (OVA)-induced allergic conjunctivitis (AC). METHODS: Conjunctival impression cytology specimens from control and patients with severe vernal keratoconjunctivitis, treated or untreated, were used to evaluate Gal-3 expression by immunocytochemistry. To investigate the mechanism of action of Gal-3, OVA-immunised BALB/c male wild-type (WT) and Gal-3 null (Gal-3-/-) mice were challenged with eye drops containing OVA on days 14-16 with a subset of animals pretreated with 0.03% tacrolimus (TC) or dexamethasone (Dex). RESULTS: Patients with AC and OVA-sensitised WT mice exhibited increased levels of Gal-3 in the conjunctiva compared with control, an effect reverted by the action of Dex and TC therapy. Twenty-four hours after the final OVA challenge, total and anti-OVA IgE levels increased significantly in the blood of OVA-sensitised WT and Gal-3-/- mice compared with controls, supporting the efficacy of the AC model. The lack of endogenous Gal-3 exacerbated the local inflammatory response, increasing the influx of eosinophils and mast cell activation. Additionally, OVA-sensitised Gal-3-/- animals exhibited increased CD4+ expression in the eyes as well as eotaxin, IL-4, IL-13 and interferon-γ levels in the tear fluid compared with WT animals. CONCLUSION: Gal-3 contributes to the pathogenesis of ocular allergy and represents a relevant therapeutic target.

Anti-inflammatory effect of galectin-1 in a murine model of atopic dermatitis.

Atopic dermatitis (AD) is caused by both dysregulated immune responses and an impaired skin barrier. Although beta-galactoside-binding protein galectin-1 (Gal-1) has immunomodulatory effects in several inflammatory disorders, therapeutic strategies based on its anti-inflammatory properties have not been explored in AD. Thus, we evaluate pharmacological treatment with Gal-1 in the progression of an ovalbumin (OVA)-induced AD-like skin lesions. The skin of OVA-immunized male BALB/c mice was challenged with drops containing OVA on days 11, 14-18 and 21-24. Additionally, in the last week, a subset of animals was treated intraperitoneally with recombinant Gal-1 (rGal-1) or dexamethasone (Dex). Treatment with rGal-1 decreased the clinical signs of dermatitis in BALB/c mice and diminished local eotaxin and IFN-γ levels. The treatment also suppressed the infiltration of eosinophils and mast cells, which was verified by reduced expression of mouse mast cell protease 6 (mMCP6) and eosinophil peroxidase (EPX). These localized effects are associated with extracellular signal-regulated kinase (ERK) activation and downregulation of endogenous Gal-1. The inhibition of disease progression induced by rGal-1 was also correlated with reduced plasma IL-17 levels. Our results demonstrate that rGal-1 is an effective treatment for allergic skin inflammation in AD and may impact the development of novel strategies for skin inflammatory diseases. KEY MESSAGES: Pharmacological treatment with rGal-1 reduces clinical signs of atopic dermatitis. Systemic treatment with rGal-1 inhibits eosinophil and mast cell influx in the skin of AD animals. rGal-1 reduced local eotaxin levels and systemic IL-17 levels. The inhibition of disease progression induced by rGal-1 was correlated with upregulation of phosphorylated ERK.

Aspectos imunológicos da infecção pelo vírus do papiloma humano (HPV) / Immunological aspects of human papiloma virus (HPV) infection

O vírus do papiloma humano (HPV-human papiloma virus) pode infectar até 80% das pessoas, principalmente as sexualmente ativas. O risco e a sintomatologia da infecção são distintos entre os gêneros. Sabe-se que existem mais de 150 sorotipos e estes são agrupados por seu tropismo. Embora a maioria das infecções siga um curso benigno, a infecção persistente por certos sorotipos pode levar ao desenvolvimento de câncer. Os sorotipos 16 e 18 estão envolvidos com uma forma grave de lesão, acarretando câncer, principalmente do colo do útero. Os sorotipos 6 e 11 são descritos como causadores de verrugas anogenitais. O vírus, de aproximadamente 8.000 pb, se instala na célula e por meio da expressão das oncoproteínas E6 e E7, levando à inibição de proteínas como a p53 e a pRB, importantes na apoptose e na parada do ciclo celular. As vacinas atuais geram imunidade contra os sorotipos 6, 11, 16 e 18. A vacina pode ser tetravalente (quatro sorotipos: 6, 11, 16 e 18) ou bivalente (16 e 18). Ambas apresentam proteção cruzada contra a infecção por sorotipos não inclusos nas vacinas, porém não possuem caráter terapêutico. O presente trabalho teve como proposta revisar os avanços sobre a infecção pelo HPV, os aspectos imunológicos e as vacinas profiláticas disponíveis.

The human papilloma virus (HPV-human papilloma virus) can infect up to 80% of people, especially sexually active. The risk of infection and symptoms are different between the sexes. It is known that there are over 150 serotypes and these are grouped by their tropism. Although most infections follow a benign course, the persistent infection with certain serotypes may lead to the development of cancer. The serotypes 16 and 18 are involved in a severe form of injury, resulting in cancer, particularly cervical cancer. Serotypes 6 and 11 are described as causes of anogenital warts. The virus, approximately 8.000 bp, it installs itself in the cell and through the expression of oncoproteins E6 and E7 leading to inhibition of proteins such as p53 and pRB, important in apoptosis and cell cycle arrest. Current vaccines generate immunity against serotypes 6, 11, 16 and 18. The vaccine can be tetravalent (four serotypes 6, 11, 16 and 18) or bivalent (16, 18). Both have cross-protection against infection by serotypes not included in the vaccines, but have no therapeutic character. This study was proposed to review progress on the HPV infection, the immunological aspects and prophylactic vaccines available.