Increased expression of inducible nitric oxide synthase in psoriatic skin and cytokine-stimulated cultured keratinocytes

Sirsjö, Allan; Karlsson, Maria; Gidlöf, Anders; Rollman, Ola; Törmä, Hans

doi:10.1111/j.1365-2133.1996.tb06963.x

Cited by 128 publications

(78 citation statements)

References 40 publications

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“…7B) and is preceded by increased release of nitric oxide as measured by nitrate and nitrite levels in the media of treated cells (Fig. 7A) (29). These enhanced nuclear levels in response to TNF␣ are concurrent with the 2-3-fold increased nitrosylation of CLIC4 (Fig.…”

Section: Association With Nuclear Import Proteins and Nuclear Residenmentioning

confidence: 84%

S-Nitrosylation Regulates Nuclear Translocation of Chloride Intracellular Channel Protein CLIC4

Malik

Shukla

Amin

et al. 2010

Journal of Biological Chemistry

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Nuclear translocation of chloride intracellular channel protein CLIC4 is essential for its role in Ca2؉ -induced differentiation, stress-induced apoptosis, and modulating TGF-␤ signaling in mouse epidermal keratinocytes. However, post-translational modifications on CLIC4 that govern nuclear translocation and thus these activities remain to be elucidated. The structure of CLIC4 is dependent on the redox environment, in vitro, and translocation may depend on reactive oxygen and nitrogen species in the cell. Here we show that NO directly induces nuclear translocation of CLIC4 that is independent of the NO-cGMP pathway. Indeed, CLIC4 is directly modified by NO through S-nitrosylation of a cysteine residue, as measured by the biotin switch assay. NO enhances association of CLIC4 with the nuclear import proteins importin ␣ and Ran. This is likely a result of the conformational change induced by S-nitrosylated CLIC4 that leads to unfolding of the protein, as exhibited by CD spectra analysis and trypsinolysis of the modified protein. Cysteine mutants of CLIC4 exhibit altered nitrosylation, nuclear residence, and stability, compared with the wild type protein likely as a consequence of altered tertiary structure. Moreover, tumor necrosis factor ␣-induced nuclear translocation of CLIC4 is dependent on nitric-oxide synthase activity. Inhibition of nitric-oxide synthase activity inhibits tumor necrosis factor ␣-induced nitrosylation and association with importin ␣ and Ran and ablates CLIC4 nuclear translocation. These results suggest that S-nitrosylation governs CLIC4 structure, its association with protein partners, and thus its intracellular distribution.CLIC4 (chloride intracellular channel protein 4) belongs to a family of differentially expressed chloride channel proteins that are largely conserved from Caenorhabditis elegans to humans.Various members have been implicated in cell signaling cascades, ranging from stimulation of chloride channel activity by CLIC3 following association with extracellular signal-regulated kinase (ERK) 7 (1) to CLIC5A that is implicated in bone resorption and HCl transport in osteoclasts, in response to phosphorylation by c-Src (2). However, a number of functions of CLIC proteins are independent of channel activity (3, 4).The best characterized of the CLIC family members is CLIC4, identified in our laboratory as a p53 and TNF␣ 2 response gene that is up-regulated during keratinocyte differentiation. CLIC4 has emerged as a crucial player in many physiological processes, including tubular morphogenesis during angiogenesis (5-7), transdifferentiation of mammary fibroblasts to myofibroblasts in response to TGF-␤ (8), and adipocyte differentiation (9). CLIC4 has been established as a significant effector of mouse and human keratinocyte differentiation, associated with G 1 cell cycle arrest and expression of differentiation markers (10).An intriguing aspect of CLIC4 biology is its role as an effector of apoptosis, including p53-and c-Myc-induced apoptosis, as well as in response to cytotoxic and ...

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Section: Association With Nuclear Import Proteins and Nuclear Residenmentioning

confidence: 84%

S-Nitrosylation Regulates Nuclear Translocation of Chloride Intracellular Channel Protein CLIC4

Malik

Shukla

Amin

et al. 2010

Journal of Biological Chemistry

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“…During the first two steps, a complicated network composed of paracrine and autocrine cytokines secreted by keratinocytes and by melanocytes, respectively, plays an important role in regulating melanogenesis in collaboration with their corresponding receptors, whose expression is also regulated by various cytokines (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). In addition, several types of cross-talk among cytokine receptor signaling pathways are involved in the enhanced proliferation and melanogenic activities of melanocytes.…”

mentioning

confidence: 99%

The Essential Role of p53 in Hyperpigmentation of the Skin via Regulation of Paracrine Melanogenic Cytokine Receptor Signaling

Murase

Hachiya

Amano

et al. 2009

Journal of Biological Chemistry

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Hyperpigmentation of the skin is characterized by increases in melanin synthesis and deposition. Although considered a significant psychosocial distress, little is known about the detailed mechanisms of hyperpigmentation. Recently, the tumor suppressor protein p53 has been demonstrated to promote ultraviolet B-induced skin pigmentation by stimulating the transcription of a melanogenic cytokine, POMC (pro-opiomelanocortin), in keratinocytes. Given that p53 can be activated by various kinds of diverse stresses, including sun exposure, inflammation, and aging, this finding led us to examine the involvement of p53 in cytokine receptor signaling, which might result in skin hyperpigmentation. Immunohistochemical and reverse transcription-PCR analyses revealed the increased expression and phosphorylation of p53 in the epidermis of hyperpigmented spots, accompanied by the higher expression of melanogenic cytokines, including stem cell factor, endothelin-1, and POMC. The involvement of p53 in hyperpigmentation was also indicated by the significantly higher expression of p53 transcriptional targets in the epidermis of hyperpigmented spots. Treatment of human keratinocytes and melanocytes with known p53 activators or inhibitors, including pifithrin-␣ (PFT), demonstrated significant increases or decreases, respectively, in the expression of melanogenic factors, including cytokines and their receptors. Additionally, PFT administration abolished stem cell factor-induced phosphorylation of mitogen-activated protein kinase in human melanocytes. Furthermore, when organ-cultured hyperpigmented spots, in vitro human skin substitutes, and mouse skin were treated with PFT or p53 small interfering RNA, the expression of melanogenic cytokines and their receptors was significantly decreased, as were levels of tyrosinase and melanogenesis. Taken together, these data reveal the essential role of p53 in hyperpigmentation of the skin via the regulation of paracrine-cytokine signaling, both in keratinocytes and in melanocytes.There are various types of hyperpigmentations (pigmented spots) of the skin characterized by increases in melanin synthesis and deposition, such as freckles, postinflammatory hyperpigmentation, UV-induced pigmentation (UV-melanoses), senile lentigines (age spots), pigmentation petaloides actinica, and melasma. These hyperpigmentations are well known to cause significant psychosocial distress, but little is known about their detailed mechanisms.Hyperpigmentation generally results from three major steps in the epidermis: the proliferation of melanocytes, the synthesis and activation of tyrosinase to produce melanin, and the transfer of melanosomes to keratinocytes (1-4). During the first two steps, a complicated network composed of paracrine and autocrine cytokines secreted by keratinocytes and by melanocytes, respectively, plays an important role in regulating melanogenesis in collaboration with their corresponding receptors, whose expression is also regulated by various cytokines (5-23). In addition, several types of c...

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“…92 NO is generated by nitric oxide synthase (NOS) enzyme and three isoforms of NOS have been identified: two constitutively expressed isoforms (endothelial NOS [eNOS] and neuronal NOS [nNOS]) and one inducible NOS (iNOS) isoform. [93][94][95] All three isoforms of NOS have been found in the skin: nNOS has been observed in keratinocytes and melanocytes 96,97 ; eNOS has been detected in basal keratinocytes, dermal fibroblasts, endothelial capillaries, and eccrine glands 98,99 ; and iNOS has been induced in keratinocytes, 100,101 dermal fibroblasts, 98 and endothelial cells. 102 NO is involved throughout the three phases of wound healing as an important regulator of angiogenesis, inflammatory response, and collagen deposition.…”

Section: 81mentioning

confidence: 99%

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

Xiao

Ahadian

Radišić

2017

Tissue Engineering Part B: Reviews

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Progress in biomaterial science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and controlling the cellular microenvironment of the wound tissue are important to improve the wound healing process. In this study, we review different biochemical (e.g., growth factors, peptides, DNA, and RNA) and biophysical (e.g., topographical guidance, pressure, electrical stimulation, and pulsed electromagnetic field) cues providing a functional and instructive acellular matrix to heal diabetic chronic wounds. The biochemical and biophysical signals generally regulate cell-matrix interactions and cell behavior and function inducing the tissue regeneration for chronic wounds. Some technologies and devices have already been developed and used in the clinic employing biochemical and biophysical cues for wound healing applications. These technologies can be integrated with smart biomaterials to deliver therapeutic agents to the wound tissue in a precise and controllable manner. This review provides useful guidance in understanding molecular mechanisms and signals in the healing of diabetic chronic wounds and in designing instructive biomaterials to treat them.

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Increased expression of inducible nitric oxide synthase in psoriatic skin and cytokine-stimulated cultured keratinocytes

Cited by 128 publications

References 40 publications

S-Nitrosylation Regulates Nuclear Translocation of Chloride Intracellular Channel Protein CLIC4

S-Nitrosylation Regulates Nuclear Translocation of Chloride Intracellular Channel Protein CLIC4

The Essential Role of p53 in Hyperpigmentation of the Skin via Regulation of Paracrine Melanogenic Cytokine Receptor Signaling

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

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