Inflammatory Cells, Cytokines and Matrix Metalloproteinases in Amicrobial Pustulosis of the Folds and other Neutrophilic Dermatoses

Marzano, Angelo Valerio; Cugno, Massimo; Trevisan, Valentina; Lazzari, Riccardo; Fanoni, Daniele; Berti, Emilio; Crosti, C.

doi:10.1177/039463201102400218

Cited by 48 publications

(36 citation statements)

References 29 publications

(33 reference statements)

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“…While it is important to mention that MMP matrilysin has been found to participate in the normal function of dermal exocrine glands (22), we speculate that MMP-2, which is a tissue degradation enzyme, is a common key event for HS due to the expansive growth of the lesions, which links to the theory that HS is due to dysregulated repair of unspecific In addition, the excessive expression of MMP-2, providing a boundless proteolytic environment, may be the inactivator of HBD2 and accordingly limit antimicrobial defence in patients with HS. Interestingly, MMP-2 has been detected previously in skin in significantly higher levels in neutrophilic dermatoses, and various studies report a role of MMP-2 in cancer (23)(24)(25)(26)(27)(28)(29). It may therefore be speculated that the increased MMP-2 expression is related to the histological picture of HS, with its proliferating epithelial strands and sinus tract formation (30).…”

Section: Discussionmentioning

confidence: 94%

Tumour Necrosis Factor-alpha and Matrix Metalloproteinase-2 are Expressed Strongly in Hidradenitis Suppurativa

Mozeika¹,

Pilmane²,

Nürnberg³

et al. 2013

Acta Derm Venerol

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Hidradenitis suppurativa is a chronic skin condition, characterized clinically by painful, recurrent, deep- seated nodules and suppuration, and histologically by hyper-trophic scarring of apocrine gland bearing skin and sinus tracts. The overall consequence of the disease is considerable tissue remodelling and the underlying alterations in innate immunity are poorly understood. The aim of this study was to evaluate the expression of human beta-defensin 2, tumour necrosis factor (TNF)-α and matrix metalloproteinase-2 in skin lesions of patients with hidradenitis suppurativa. A total of 14 skin samples from patients and 2 skin samples from healthy volunteers were evaluated by immunohistochemistry. Human beta-defensin 2 was negative in 12/14 specimens. Elevated expression of metalloproteinase-2 was observed in keratinocytes, fibroblasts and inflammatory cells in dermis, sweat glands, hair follicles and sinus tracts, suggesting a key role for hidradenitis suppurativa pathogenesis. Decreased human beta-defensin 2 in the presence of inflammatory (TNF-α-containing) cells suggests a decreased innate immunity in hidradenitis suppurativa-affected skin.

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Section: Discussionmentioning

confidence: 94%

Tumour Necrosis Factor-alpha and Matrix Metalloproteinase-2 are Expressed Strongly in Hidradenitis Suppurativa

Mozeika¹,

Pilmane²,

Nürnberg³

et al. 2013

Acta Derm Venerol

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“…Nevertheless, differences in the balance of Treg/Th17, the relative intensity of the expression of cytokines and MMPs, and a different genetic background may in part justify the different patterns of skin aggression in these diseases. 14,17,19 PG also shares many features with auto-inflammatory disorders, including the chronic remitting course, the dysregulation of the innate immune system with neutrophil recruitment and activation, and a role for excessive cytokine production. 8 Additionally, PG lesions are almost always observed in patients with PAPA syndrome, a rare inherited auto-inflammatory syndrome with excessive IL1 production.…”

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confidence: 99%

Pyoderma gangrenosum: challenges and solutions

Gameiro¹,

Pereira²,

Cardoso³

et al. 2015

OTT

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Pyoderma gangrenosum (PG) is a rare disease, but commonly related to important morbidity. PG was first assumed to be infectious, but is now considered an inflammatory neutrophilic disease, often associated with autoimmunity, and with chronic inflammatory and neoplastic diseases. Currently, many aspects of the underlying pathophysiology are not well understood, and etiology still remains unknown. PG presents as painful, single or multiple lesions, with several clinical variants, in different locations, with a non specific histology, which makes the diagnosis challenging and often delayed. In the classic ulcerative variant, characterized by ulcers with inflammatory undermined borders, a broad differential diagnosis of malignancy, infection, and vasculitis needs to be considered, making PG a diagnosis of exclusion. Moreover, there are no definitively accepted diagnostic criteria. Treatment is also challenging since, due to its rarity, clinical trials are difficult to perform, and consequently, there is no "gold standard" therapy. Patients frequently require aggressive immunosuppression, often in multidrug regimens that are not standardized. We reviewed the clinical challenges of PG in order to find helpful clues to improve diagnostic accuracy and the treatment options, namely topical care, systemic drugs, and the new emerging therapies that may reduce morbidity.

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“…However, adverse effects of PMNs such as the promotion of aggressive tumor growth and an increased metastatic potential have been described, for example, in mammary cancer [12,13]. An attractive hypothesis is that PMN-derived matrix-degrading proteases such as the metalloproteinases (MMP) 1, MMP2, and MMP9 or the neutrophil elastase [14][15][16] …”

mentioning

confidence: 99%

Polymorphonuclear neutrophils promote dyshesion of tumor cells and elastase‐mediated degradation of E‐cadherin in pancreatic tumors

et al. 2012

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Pancreatic ductal adenocarcinoma (PDAC) presenting with a micropapillary growth pattern is frequently associated with a prominent neutrophil infiltration into the tumor. The relevance of neutrophil infiltrates for tumor progression, however, is still debated. To gain insight into the role of polymorphonuclear neutrophils (PMNs) in PDAC, we assessed their effect on pancreatic tumor cells grown in vitro as monolayers. Time-lapse video microscopy showed a PMN-induced dyshesion of the tumor cells, and subsequent experiments revealed that this dyshesion was due to PMN elastase-mediated degradation of E-cadherin, an adhesion molecule that mediates the intercellular contact of the tumor cells. E-cadherin degradation by elastase or -(for comparison) down-modulation by specific siRNA, significantly increased the migratory capacity of the pancreatic tumor cells, leading to the hypothesis that PMNs could contribute to the invasive tumor growth. To address this issue, biopsies of patients with PDAC (n = 112) were analyzed. We found that E-cadherin expression correlated negatively with PMN infiltration, compatible with the notion that E-cadherin is cleaved by PMN-derived elastase, which in turn could result in the dispersal of the tumor cells, enhanced migratory capacity and thus invasive tumor growth.Keywords: E-cadherin r Invasion r Pancreatic cancer r PMN elastase r Polymorphonuclear neutrophils Supporting Information available online IntroductionPancreatic ductal adenocarcinoma (PDAC) is the fourth most common cancer-related death in Western countries with a devasCorrespondence: Prof. Gertrud M. Hänsch e-mail: Maria.Haensch@urz-uni-heidelberg.de tating prognosis of an overall 5-year survival rate of less than 5% [1]. The dismal prognosis is due to the aggressive and invasive tumor growth, early metastasis, and resistance to radiation and chemotherapy [1,2]. A hallmark of pancreatic cancer is the distinct intratumoral inflammatory reaction, with an infiltration of T lymphocytes, macrophages [3][4][5]. Infiltration of polymorphonuclear neutrophils (PMNs) was described in PDAC and cancers of the periampullary region, where intratumor PMN infiltration was C 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 3370 Matthias M. Gaida et al. Eur. J. Immunol. 2012. 42: 3369-3380 associated with a "micropapillary" and "scattered" growth pattern, poor histological differentiation and a poor prognosis [6,7]. The role of the PMNs in the tumor progression is controversially discussed, and not yet conclusively understood [3,8,9]. PMNs have the potential to kill tumor cells, either directly [10] or by Ab-dependent cell-mediated cytotoxicity [11]. However, adverse effects of PMNs such as the promotion of aggressive tumor growth and an increased metastatic potential have been described, for example, in mammary cancer [12,13]. An attractive hypothesis is that PMN-derived matrix-degrading proteases such as the metalloproteinases (MMP) 1, MMP2, and MMP9 or the neutrophil elastase [14][15][16] Results PMN-derived elastase...

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Inflammatory Cells, Cytokines and Matrix Metalloproteinases in Amicrobial Pustulosis of the Folds and other Neutrophilic Dermatoses

Cited by 48 publications

References 29 publications

Tumour Necrosis Factor-alpha and Matrix Metalloproteinase-2 are Expressed Strongly in Hidradenitis Suppurativa

Tumour Necrosis Factor-alpha and Matrix Metalloproteinase-2 are Expressed Strongly in Hidradenitis Suppurativa

Pyoderma gangrenosum: challenges and solutions

Polymorphonuclear neutrophils promote dyshesion of tumor cells and elastase‐mediated degradation of E‐cadherin in pancreatic tumors

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