Eosinophil-specific deletion of IκBα in mice reveals a critical role of NF-κB-induced Bcl-xL for inhibition of apoptosis.

Eosinophils are associated with type 2 immune responses to allergens and helminths. They release various proinflammatory mediators and toxic proteins on activation and are therefore considered proinflammatory effector cells. Eosinophilia is promoted by the cytokines interleukin (IL)-3, IL-5, and granulocyte macrophage-colony-stimulating factor (GM-CSF) and can result from enhanced de novo production or reduced apoptosis.

Primary cutaneous follicle center lymphoma with diffuse CD30 expression: a report of 4 cases of a rare variant.

Background: CD30 is expressed in aggressive and Epstein-Barr virus-associated forms of B-cell non-Hodgkin lymphomas, but is rarely expressed by the majority of tumor cells in primary cutaneous B-cell lymphomas (CBCLs). The expression of CD30 in CBCLs may be at risk for misinterpretation as an unequivocal indicator of a highly aggressive form of the disease.

Objective: We report 4 cases of low malignant primary cutaneous follicle center lymphoma (PCFCL) with diffuse and strong expression of CD30 by the majority of neoplastic cells.

Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties.

Cell-type plasticity within a tumor has recently been suggested to cause a bidirectional conversion between tumor-initiating stem cells and nonstem cells triggered by an inflammatory stroma. NF-κB represents a key transcription factor within the inflammatory tumor microenvironment. However, NF-κB's function in tumor-initiating cells has not been examined yet.

Constitutive activity of NF-kappa B in myeloid cells drives pathogenicity of monocytes and macrophages during autoimmune neuroinflammation.

The NF-κB/REL-family of transcription factors plays a central role in coordinating the expression of a wide variety of genes controlling immune responses including autoimmunity of the central nervous system (CNS). The inactive form of NF-κB consists of a heterodimer which is complexed with its inhibitor, IκB. Conditional knockout-mice for IκBα in myeloid cells (lysMCreIκBα(fl/fl)) have been generated and are characterized by a constitutive activation of NF-κB proteins allowing the study of this transcription factor in myelin-oligodendrocyte-glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE), a well established experimental model for autoimmune demyelination of the CNS.

Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells.

Fumarates improve multiple sclerosis (MS) and psoriasis, two diseases in which both IL-12 and IL-23 promote pathogenic T helper (Th) cell differentiation. However, both diseases show opposing responses to most established therapies. First, we show in humans that fumarate treatment induces IL-4-producing Th2 cells in vivo and generates type II dendritic cells (DCs) that produce IL-10 instead of IL-12 and IL-23.

Myeloid IκBα deficiency promotes atherogenesis by enhancing leukocyte recruitment to the plaques.

Activation of the transcription factor NF-κB appears to be involved in different stages of atherogenesis. In this paper we investigate the role of NF-κB inhibitor IκBα in atherosclerosis. Myeloid-specific deletion of IκBα results in larger and more advanced lesions in LDL-R-deficient mice without affecting the compositional phenotype of the plaques or systemic inflammatory markers in the plasma.

Chitin modulates innate immune responses of keratinocytes.

Background: Chitin, after cellulose the second most abundant polysaccharide in nature, is an essential component of exoskeletons of crabs, shrimps and insects and protects these organisms from harsh conditions in their environment. Unexpectedly, chitin has been found to activate innate immune cells and to elicit murine airway inflammation. The skin represents the outer barrier of the human host defense and is in frequent contact with chitin-bearing organisms, such as house-dust mites or flies.

The NFĸB pathway inhibitors Bay 11-7082 and parthenolide induce programmed cell death in anucleated Erythrocytes.

The preclinical compounds Bay 11-7082 and parthenolide trigger apoptosis, an effect contributing to their antiinflammatory action. The substances interfere with the activation and nuclear translocation of nuclear factor NFκB, by inhibiting NFκB directly (parthenolide) or by interfering with the inactivation of the NFκB inhibitory protein IκB-α (Bay 11-7082). Beyond that, the substances may be effective in part by nongenomic effects.

[Verrucous squamous cell carcinoma complicating hypertrophic lichen planus. Three case reports and review of the literature].

Lichen planus is a chronic mucocutaneous T-cell-mediated disease, whose cause is still unknown. The first case of lichen planus that transformed into squamous cell carcinoma was reported in 1903. We present three patients in whom squamous cell carcinomas were identified in chronic lichen planus.

What is really in control of skin immunity: lymphocytes, dendritic cells, or keratinocytes? facts and controversies.

The pathophysiology of atopic dermatitis is still under discussion. Although it is widely accepted that environmental factors and a genetic predisposition are essential, the role of the innate and adaptive immune system and the functional cascade of the cells involved is still unclear. A concept that integrates all immune cells as equally essential has allure.

Complementary therapy for atopic dermatitis and other allergic skin diseases: facts and controversies.

The term complementary or alternative medicine encompasses numerous diverse therapeutic concepts, ranging from as herbal medicine, diet with essential fatty acids, and probiotics, to acupuncture. The main focus of these treatment methods is inflammatory skin disease, in particular atopic dermatitis. Although integrative medicine enjoys increasing popularity, particularly in industrialized countries, clinical studies that meet the double-blind, placebo-controlled standard are rare or nonexistent.

[Ulcers following therapy with hydroxyurea. Three case reports and review of the literature].

Hydroxyurea is frequently used for therapy of myeloproliferative disorders. One cutaneous side-effect is painful, therapy-resistant ulcers which have bizarre configurations and occur at atypical sites for venous ulcers. Improvement or healing often first occurs when hydroxyurea is discontinued.

The potential role of c-Jun activation in patients with cutaneous lichen planus.

c-Jun, a component of the activating protein-1 transcription factor family, has been known to play an important role in the control of cell proliferation. It is also suspected to be a critical mediator of tumor promotion. However, investigations of c-Jun activation patterns in inflammatory and inflammatory transforming skin diseases have not been described so far.

[Diagnostic pitfall: basal cell carcinoma arising in a therapy-resistant chronic venous ulcer of the lower leg].

History: A 96-year-old woman attended our department with an ulcer on the lower leg. It looked typical of an ulcer due to chronic venous insufficiency an had been resistant to treatment for 20 years.

Investigations: On the left lower leg there was a 5 x 5 cm ulcer with a sharply demarkated border.

IkappaBalpha is required for marginal zone B cell lineage development.

Inactivation of members of the nuclear factor-kappaB (NF-kappaB) family results in the decrease or defect of marginal zone B (MZB) cells. It is not known which inhibitors of the NF-kappaB family (IkappaB) are required for MZB cell development. Here, we show that mice with B cell-specific inactivation of the main NF-kappaB inhibitor IkappaBalpha have a marked decrease of MZB cells and their presumed precursors.

[Cathelicidin LL-37. A central factor in the pathogenesis of inflammatory dermatoses?].

Keratinocytes produce and secrete antimicrobial peptides which function as endogenous antibiotics and as signaling molecules within the cutaneous innate immune system. Recent studies demonstrate that the antimicrobial peptide cathelicidin LL-37 plays an important role in the pathogenesis of atopic eczema, rosacea and psoriasis. Whereas skin in atopic eczema shows decreased cathelicidin expression which leads to increased susceptibility to superinfection in those patients, overabundant expression of cathelicidin peptide fragments causes inflammation in rosacea.

Role of NF-kappaB/RelA and MAPK pathways in keratinocytes in response to sulfur mustard.

Sulfur mustard (SM) is a strong vesicant that has been used as a chemical warfare agent. To understand the molecular mechanisms that underlie the inflammatory skin reaction in response to SM, we analyzed the activation pattern of the NF-kappaB and mitogen-activated protein kinase (MAPK) pathways. Keratinocytes responded with an induction of the canonical NF-kappaB pathway, including activation of IkappaB kinase 2, followed by phosphorylation and degradation of IkappaBalpha and of the transactivating subunit RelA at Ser536.