Role of neutrophils in induction of acute inflammation in T‐cell‐mediated immune dermatosis, psoriasis: A neutrophil‐associated inflammation‐boosting loop

Abstract

A growing body of evidence has indicated that T-cell-mediated immunity plays an important role in triggering and maintenance of psoriatic lesions. In this review we present our own experimental results as well as those from the literature related to the pathomechanism of the development of inflammatory changes in psoriatic lesions. First of all it is important to acknowledge the fact that psoriatic lesions are not uniform as assumed by many authors but that they are actually rather heterogeneous both clinically and histologically even within the same plaques. Lymphokines produced by activated T cells in psoriatic lesions have a strong influence on the proliferation of the epidermis, whose stimulated kertinocytes released several cytokines, which in turn enhance the activation state of T cells. Thus, they form a vicious cycle, a T-cell-mediated inflammationsustaining loop. Although the interaction between T-cell-mediated immunity and epidermal keratinocytes may well explain the maintenance of background ''chronic'' inflammatory changes diffusely observed throughout psoriatic lesions, it is not enough to explain the island-like, ''acute'' inflammatory changes observed within and at the border of the plaque lesions. Characteristic neutrophil accumulation under the stratum corneum can be observed in the highly inflamed and therapeutically recalcitrant areas of psoriatic lesions. They are chemotactically attracted and activated there by synergistic action of chemokines, IL-8 and Gro-a released by the stimulated keratinocytes, and particularly C5a/C5a des arg produced via the alternative complement pathway activation possibly on the surface of corneocytes. In this review, we emphasize that the accumulation of neurophils is not simply a passive event. We think that those stimulated neutrophils are able to influence not only the growth that may well explain the localized ''acute'' inflammatory changes scate-mail: terui/mail.cc.tohoku.ac.jp tered over the ''chronic'' psoriatic plaques as well as in the acutely inflamed lesions of pustular psoriasis.

Clinico-biochemical correlation between psoriasis and lipid profile

“…Psoriasis is now considered a systemic inflammatory disease, with Th-1 cells, Th-17 cells and inflammatory cytokines contributing to its pathogenesis. [20][21][22][23][24] Furthermore, in agreement with previous findings suggesting of abnormal lipoprotein metabolism may be related to the high incidence of atherosclerosis in psoriasis. Hypertriglyceridemia secondary to VLDL is associated with both procoagulant and prothrombotic factors in the blood.…”

Hydrogen sulfide inhibits IL-8 expression in human keratinocytes via MAP kinase signaling

“…pERKs show the classical nuclear localization, while keratinocytes of normal skin show low pERKs levels with a main cytoplasmic localization. 21,41,42 According with the evidence that biologically active IL-8 is produced in large amounts in psoriatic skin 3,43 we have observed a strong immunoreactivity of the epidermal layer to anti-IL-8 antibody. When we treated topically a psoriatic lesion with NaHS kept in the same concentration range found in most balneotherapies, pERKs expression in the lesion was clearly reduced at both nuclear and cytoplasmic levels, paralleled by a concomitant reduction of IL-8 expression.…”

The Increased Expression of Matrix Metalloproteinase-9 Messenger RNA in the Non-lesional Skin of Patients with Large Plaque Psoriasis Vulgaris

“…Psoriasis is a chronic inflammatory dermatosis that is characterized by epidermal hyperplasia, angiogenesis and chronic inflammatory infiltrates, and the latter are composed of activated type 1 T cells, dendritic cells and neutrophils [1][2][3][4][5] . Several gene expression studies have suggested a coordinated activation of the type 1 inflammatory axis in the skin lesions of patients with psoriasis vulgaris along with an increased production of interferon (IFN)-γ-inducing inflammatory mediators/chemokines that sustain the chronic influx of leukocytes [6][7][8] [MIG] and inducible nitric oxide synthase [iNOS], S100A2), only a difference in the IL-18 mRNA expression was previously observed between Western large plaque (LP) psoriasis patients (more than 5 cm lesions are typical) and Asian small plaque (SP) psoriasis patients (1∼2 cm lesions are typical) 9 .…”