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Woan-Ruoh Lee

Publications and source records attributed to Woan-Ruoh Lee.

At least 19 recordsLinked to original sources
PubMed2006

Induction of TIMP-1 and HSP47 synthesis in primary keloid fibroblasts by exogenous nitric oxide.

BACKGROUND: The excessive accumulation of extracellular matrix is a hallmark of many fibrotic diseases, including the hypertrophic scar and keloid. Recent reports from this research team had shown that exogenous nitric oxide (NO) participates in the keloid formation; however, its role on the synthesis of fibrotic factor (TGF-beta1, TIMP-1 and HSP47) in the keloid fibroblasts (KF) remained unclear. OBJECTIVE: In this study, to better define the potential effect of exogenous NO on the expression of fibrotic factors in KF, the enhancing effect of exogenous NO, released from a NO donor, on the synthesis of fibrotic factors in KF was investigated. METHODS: The seven primary KF cultures were set up to measure the effect of exogenous NO on enhancing the expression of fibrotic factor. RESULTS: Elevation of cellular cGMP levels was observed to be induced by NO or blocked by the hydrolysis activity of phosphodiesterase (PDE) by the PDE inhibitor. The elevated levels of cellular cGMP were noted to enhance the expression of TIMP-1 and HSP47 in KF. Exogenous NO was found to significantly accelerate the production of TIMP-1 and HSP47 in the seven primary KFs with a corresponding increase in the production of TGF-beta1. CONCLUSION: The results have led to a conclusion, that is: the excess collagen formations in the keloid lesion may be attributed to the NO/cGMP signal pathway by initiating a rapid increase in the expression of TGF-beta1, TIMP-1 and HSP47 in the KF cells.

Adult↗
PubMed2006

Exogenous nitric oxide stimulated collagen type I expression and TGF-beta1 production in keloid fibroblasts by a cGMP-dependent manner.

Keloids arise from the aberrant wound healing process and nitric oxide (NO) plays an important role in the inflammation stage of wound healing. In order to better define the potential effect of NO/cGMP signal pathway in the keloid pathogenesis, the enhancing effect of exogenous NO (released from NO donor) on collagen expression in the keloid fibroblast (KF) as well as on the induction of collagen type I protein and TGF-beta1 expression in the KF were studied in this investigation. The DETA NONOate, an NO donor, was added to the KF, as the exogenous NO, to release NO in the culture medium. The expression of collagens was then determined by assaying the total soluble collagens and collagen type I in the KF. The cellular concentration of cGMP was measured by EIA in the KF. Exogenous NO was found to enhance the expression of collagens and elevate the cellular levels of cGMP. Moreover, to evaluate the effect of the elevated cellular cGMP levels on the expression of collagen and TGF-beta1, both cGMP and TGF-beta1 were measured by ELISA. The inhibitors for phosphodiesterase (PDE), such as IBMX (3-isobutyl-1-methylxanthine), Vinpocetine, EHNA, Milrinone and Zapriast, which have been reported to reduce the ability of PDE and subsequently produce an increase of cellular cGMP, induce the production of autocrine TGF-beta1 as well as the synthesis of collagen in the KF. In this investigation, the inhibition of the PDE enzyme activity was observed to enhance the effect on the collagen synthesis, and was induced by exogenous NO. Taken together, these results have suggested that the NO/cGMP pathway could positively influence the progression of keloid formation, via the TGF-beta1 expression in the KF.

1-Methyl-3-isobutylxanthine↗
PubMed2006

Erbium:YAG laser-mediated oligonucleotide and DNA delivery via the skin: an animal study.

Topical delivery of antisense oligonucleotides (ASOs) and DNA is attractive for treatment of skin disorders. However, this delivery method is limited by the low permeability of the stratum corneum (SC). The objective of this study was to enhance and optimize the skin absorption of gene-based drugs by an erbium:yttrium-aluminum-garnet (Er:YAG) laser. The animal model utilized nude mice. In the in vitro permeation study, the Er:YAG laser treatment produced a 3-30-fold increase in ASO permeation which was dependent on the laser fluence and ASO molecular mass used. The fluorescence microscopic images showed a more-significant localization of a 15-mer ASO in the epidermis and hair follicles after laser application as compared with the control. The expressions of reporter genes coding for beta-galactosidase and green fluorescent protein (GFP) in skin were assessed by X-gal staining and confocal laser scanning microscopy. The SC ablation effect and photomechanical waves produced by the Er:YAG laser resulted in DNA expression being extensively distributed from the epidermis to the subcutis. The GFP expression in 1.4 J/cm2-treated skin was 160-fold higher than that in intact skin. This non-invasive, well-controlled technique of using an Er:YAG laser for gene therapy provides an efficient strategy to deliver ASOs and DNA via the skin.

Administration, Topical↗
PubMed2006

Inhibition of inflammatory nitric oxide production and epidermis damages by Saccharomycopsis Ferment Filtrate.

BACKGROUND: Yeast extracts have been shown to perform anti-inflammatory and cytoprotective activities. However, the effects of yeast extracts on lipopolysaccharide (LPS)-induced nitric oxide (NO) production and epidermal damages are still unclear. OBJECTIVE: To investigate the effect of Saccharomycopsis Ferment Filtrate (SFF) on LPS-induced NO production in RAW264.7 macrophages and epidermal damages. METHOD: RAW264.7 cells are incubated with LPS (25 ng/mL) and different concentrations of SFF. The amount of NO production is detected by Griess reaction. Additionally, the expression of inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) are detected by Western blotting. Artificial epidermis is also used to mimic the in vivo condition to investigate the protective effects of SFF on LPS- or ultraviolet radiation (UVR)-induced damages by histology and electron microscopy. RESULTS: The results show that SFF addition inhibits LPS-induced NO production and iNOS protein expression in a concentration-dependent manner without notable cytotoxicity in RAW264.7 cells, and induction of HO-1 protein expression by SFF was observed. Interestingly, both HO-1 inducers, hemin and CoCl2, significantly attenuated LPS-induced NO production and iNOS protein expression. The addition of CoCl2 potentiated the inhibitory effect of SFF on LPS-induced NO production. It seems that HO-1 protein participates in SFF inhibition of LPS-induced NO production. Furthermore, SFF exhibits significant protective effect on LPS- or UVR-induced damages in the artificial epidermis via histological and electron microscopic observations. CONCLUSION: This study provided the first evidence to indicate the beneficial effects of SFF in preventing NO production in macrophages and damages in epidermis, respectively. It suggests that SFF possesses potential to be further developed.

Animals↗
PubMed2006

Nitric oxide produced by iNOS is associated with collagen synthesis in keloid scar formation.

Nitric oxide (NO) has emerged as an important mediator of many physiological functions. Recent reports have shown that NO participates in the wound healing process, however, its role in keloid formation remains unclear. This study aimed to investigate the effect of NO on keloid fibroblasts (KF) and to determine the levels of inducible nitric oxide synthase (iNOS) expression in clinical specimens of keloid. Scar tissue from seven keloid patients with matched perilesion skin tissue controls was studied for inducible nitric oxide synthase expression and location. In addition, primary keloid and normal scar skin fibroblast cultures were set up to investigate the effects of NO in inducing collagen type I expression. Inducible nitric oxide synthase expression, and NO production were elevated in keloid scar tissues but not in matched perilesion skin tissues. Furthermore, exposure of KF to exogenous NO resulted in increased expression of collagen type I in a dose-dependent manner. NO exposure also induced time-course dependent collagen I expression that peaked at 24h in KF. Taken together, these results indicate that excess collagen formations in keloid lesion may be attributed to iNOS overexpression.

Cells, Cultured↗
PubMed2006

Effect of liposome encapsulation of tea catechins on their accumulation in basal cell carcinomas.

BACKGROUND: (-)-Epigallocatechin gallate (EGCG), the main active polyphenol in green tea, is associated with antioxidant and anticancer activities. OBJECTIVE: The aim of this study was to evaluate the feasibility of using liposomes for intratumor distribution of EGCG and its derivative, (+)-catechin. METHOD: Liposomes containing egg phosphatidylcholine, cholesterol, or anionic surfactant in the presence of 15% ethanol were prepared. The physicochemical characteristics including vesicle size, zeta potential, drug entrapment, and drug release of liposomal formulations were determined. The liposomes containing EGCG were injected into basal cell carcinomas (BCCs), melanomas, and colon tumors to examine the tumor uptake of the drug. Liposomes were also incubated with a given number of BCC cells, and the cell viability was estimated. RESULT: Almost no drug molecules were observed when free EGCG was administered to BCCs. EGCG encapsulated in liposomes with deoxycholic acid (DA) and ethanol increased drug deposition by 20-fold as compared to the free form. The larger vesicle size of this formulation was suggested to be the predominant factor governing this enhancement. The liposomes without ethanol showed low or negligible enhancement on EGCG uptake in BCCs. Liposomes protected EGCG from degradation, resulting in the induction of greater BCC death compared to that by free EGCG at lower concentrations. CONCLUSION: These results suggest that the intratumor injection of liposomes containing EGCG with moderate modification is an effective approach for increasing EGCG deposition in BCCs.

Animals↗
PubMed2006

In vitro percutaneous absorption and in vivo protoporphyrin IX accumulation in skin and tumors after topical 5-aminolevulinic acid application with enhancement using an erbium:YAG laser.

5-aminolevulinic acid (ALA) is used as a precursor of protoporphyrin IX (PpIX) for photodynamic therapy (PDT) of superficial skin cancers and subcutaneous metastases of internal malignancies. The permeability of ALA across intact skin is always low, making it difficult to achieve the desired therapeutic benefits. Hence new methods for enhancing ALA permeation are urgently needed. The aim of this study was to determine the in vivo kinetics of PpIX generation in mouse tissues after topical ALA application enhanced by an erbium (Er):yttrium-aluminum-garnet (YAG) laser. The in vitro permeation of ALA was also used to screen the optimal method for the in vivo study. The efficacy of the improved drug delivery was determined as a function of various laser fluences and cancer models. ALA applied to laser-treated skin produced a higher accumulations of PpIX within superficial skin and subcutaneous tumors as compared to those of the non-treated group (t-test, p < 0.05). The enhancement ratios (ER) of laser-treated skin ranged from 1.7 to 4.9 times as compared to the control depending to the fluences used. The enhanced PpIX level of laser-treated skin was generally more pronounced in normal and lesional skin than in subcutaneous nodular tumors. Confocal laser scanning microscopy (CLSM) of laser-treated skin revealed intense red fluorescence within the epidermis and upper dermis, and a much-weaker fluorescence within the bottom layers of the skin. On the other hand, the fluorescence intensity of the control group was much lower than that of laser-treated group. The barrier properties of the skin irradiated by the laser had completely recovered within 3 days. Pretreatment of skin using an Er:YAG laser was useful in increasing the amount of Pp IX within skin tumors.

Administration, Cutaneous↗
PubMed2006

Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions.

The anticonvulsant carbamazepine (CBZ) frequently causes cutaneous adverse drug reactions (cADRs), including maculopapular eruption (MPE), hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We reported that SJS/TEN caused by CBZ is strongly associated with the HLA-B*1502 gene in Han Chinese. Here, we extended our genetic study to different types of CBZ-cADRs (91 patients, including 60 patients with SJS/TEN, 13 patients with hypersensitivity syndrome and 18 with maculopapular exanthema versus 144 tolerant controls). We used MALDI-TOF mass spectrometry to screen the genetic association of 278 single nucleotide polymorphisms (SNPs), which cover the major histocompatibility complex (MHC) region, tumor necrosis factor-alpha, heat shock protein and CBZ-metabolic enzymes, including CYP3A4, 2B6, 2C8, 2C9, 1A2 and epoxide hydrolase 1. In addition, we genotyped 20 microsatellites in the MHC region and performed HLA-typing to construct the recombinant map. We narrowed the susceptibility locus for CBZ-SJS/TEN to within 86 kb flanking the HLA-B gene on the extended B*1502 haplotype, and confirmed the association of B*1502 with SJS/TEN [Pc=1.6x10, odds ratio (OR)=1357; 95% confidence interval (CI)=193.4-8838.3]. By contrast to CBZ-SJS/TEN, HLA-B*1502 association was not observed in the MPE or HSS groups: MPE was associated with SNPs in the HLA-E region and a nearby allele, HLA-A*3101 (Pc=2.2x10, OR=17.5; 95% CI=4.6-66.5), and HSS with SNPs in the motilin gene (Pc=0.0064, OR=7.11; 95% CI=3.1-16.5) located terminal to the MHC class II genes. No SNPs in genes involved in CBZ metabolism were associated with CBZ-induced cADRs. Our data suggest that HLA-B*1502 could contribute to the pathogenesis of CBZ-SJS/TEN, and that genetic susceptibility to CBZ-induced cADRs is phenotype-specific.

Anticonvulsants↗
PubMed2006

Microdermabrasion as a novel tool to enhance drug delivery via the skin: an animal study.

BACKGROUND: Microdermabrasion is a widely performed skin rejuvenation procedure. It can partly ablate and homogenize the stratum corneum (SC) layers. OBJECTIVE: The effect of microdermabrasion treatment on the skin permeation of hydrophilic and lipophilic drugs was examined in this study. METHODS: 5-Fluorouracil (5-FU) and clobetasol 17-propionate were used as the hydrophilic and lipophilic permeants, respectively. In vitro skin delivery using porcine skin and in vivo topical application employing nude mouse as the animal model were both used to examine the effect of microdermabrasion. The vacuum pressures used in this study (15-25 cmHg) were much lower than those used for therapeutic purposes. RESULTS: The 5-FU permeation across microdermabrasion-treated skin was 8- to 24-fold higher than that across intact skin and depended on differences in treatment pressure and duration. An intensity of 15 cmHg for 10 seconds showed the greatest enhancement of 5-FU delivery via the skin. In contrast to the results for 5-FU, microdermabrasion reduced the skin permeation and deposition of topically applied clobetasol. The partitioning effect of clobetasol from the vehicle to the SC may have predominated this result. Microdermabrasion also enhanced the skin delivery of the hydrophilic 5-aminolevulinic acid (ALA). Confocal laser scanning microscopy (CLSM) of microdermabrasion-treated skin revealed intense red fluorescence of ALA-transformed protoporphyrin (PpIX) within the epidermis and upper dermis. CONCLUSIONS: Microdermabrasion can improve the skin permeation of hydrophilic molecules.

Administration, Topical↗
PubMed2004

Transdermal delivery of macromolecules by erbium:YAG laser.

The aim of this study was to assess the effect of molecular weight (MW) on the transdermal delivery of macromolecules by erbium:yttrium-aluminum-garnet (Er:YAG) laser treatment. Fluorescein isothiocyanate (FITC)-labeled dextran (FD) of increasing MWs (4.4, 19.4, 38, and 77 kDa) was used as the model macromolecules to investigate the skin permeation in vitro. Fluorescence microscopy and scanning electron microscopic (SEM) images were utilized to examine the transport mechanisms of the macromolecules via the skin after laser treatment. The results indicate a significant increase in the permeation of FITC and FD across skin treated by the laser. The MWs of macromolecules and laser fluences were found to play important roles in controlling macromolecular absorption. Transdermal delivery of FD with a MW of at least 77 kDa could be achieved with laser treatment. Follicular routes were significant for FITC permeation, whereas intercellular pathways played important roles on the delivery of FD. Ablation of the stratum corneum (SC) layer, photomechanical stress on intercellular regions, and alterations of the morphology and arrangement of corneocytes are possible mechanisms of how the Er:YAG laser promotes macromolecular delivery. No alteration of viable skin morphology was observed after laser treatment and the partly ablation of the SC may be reversible. Hexameric insulin showed higher skin permeation than did FD with similar MWs (38 kDa) with laser enhancement. From the study presented herein, it is concluded that the Er:YAG laser can be effective for transdermal delivery of macromolecules and hydrophilic permeants such as peptides and protein-based drugs.

Administration, Cutaneous↗
PubMed2004

Milium-like syringoma: a case study on histogenesis.

BACKGROUND: Milium-like syringoma is a variant of syringoma first described in 1987. Only few cases have been reported in the literature. It may be misleading clinically, and its histogenesis has not been clarified. CASE REPORT: We present a case of periorbital milium-like syringoma, with studies on the histopathologic, histochemical, and immunohistochemical features. RESULTS: Histology showed a large keratin-filled cyst in the upper portion of the lesion approximating the epidermis. Serial sections revealed that the cyst connected with the underlying syringomatous epithelial strands. Melanin was absent in the wall of the cyst, as demonstrated by Fontana-Masson stain. Cytokeratin 7 was expressed neither in the milia nor in the solid epithelial parts. Carcinoembryonic antigen (CEA) reactivity was seen in the luminal cells of the keratinous cysts. However, in the largest keratin-filled cyst clinically suggesting a milium, only the lower half of the cyst was positive for CEA. These results proved that the milia were part of syringoma with eccrine duct differentiation. Fusion of the upper half of the largest cyst with the epidermis may explain the absence of CEA positivity in this part, analogous with eccrine duct milia. Review of the literature indicated that this variant of syringoma occurs more often in Asians. CONCLUSION: We present evidence, and propose the histogenesis of milium-like syringoma, that it is a variant of syringoma with a prominent cystic component showing features of eccrine duct milia. Recognition of its nature is of therapeutic significance. Further studies are required to verify its clinical characteristics as compared with ordinary syringomas.

Adult↗
PubMed2004

Erbium:YAG laser pretreatment accelerates the response of Bowen's disease treated by topical 5-fluorouracil.

BACKGROUND: Topical 5-fluorouracil (5-FU) is a standard treatment for Bowen's disease. However, its efficacy may be limited by the presence of stratum corneum. The Er:YAG laser has shown a dramatic enhancement effect on the delivery of 5-FU in vitro by ablation of the stratum corneum. The efficacy of laser-assisted delivery of 5-FU has not been tested in human. OBJECTIVE: To see whether Er:YAG laser pretreatment can improve the efficacy of topical 5-FU in the treatment of Bowen's disease. METHODS: Three target lesions from a patient with multiple Bowen's disease were selected for a half-side comparison study. The Er:YAG laser was used to remove the cornified layer on one side of each lesion, followed by twice-daily application of 5-FU cream to both sides. Clinical and histologic responses were compared. RESULTS: Lesions pretreated with the Er:YAG laser showed more rapid clinical and histologic responses to topical 5-FU than those treated with 5-FU alone. Evaluation at 9 months after treatment showed no recurrences of lesions on both sides. CONCLUSIONS: Our preliminary study demonstrates that this Er:YAG laser-assisted modality is effective and shows accelerated clinical response and shortened treatment time compared with topical 5-FU as a single treatment.

Administration, Topical↗
PubMed2003

Lasers and microdermabrasion enhance and control topical delivery of vitamin C.

The objective of this study was to evaluate the ability of lasers and microdermabrasion, both of which are skin resurfacing modalities, to enhance and control the in vitro skin permeation and deposition of vitamin C. The topical delivery of magnesium ascorbyl phosphate, the pro-drug of vitamin C, was also examined in this study. All resurfacing techniques evaluated produced significant increases in the topical delivery of vitamin C across and/or into the skin. The erbium:yttrium-aluminum-garnet (Er:YAG) laser showed the greatest enhancement of skin permeation of vitamin C among the modalities tested. The laser fluence and spot size were found to play important parts in controlling drug absorption. An excellent correlation was observed in the Er:YAG laser fluence and transepidermal water loss, which is an estimation of skin disruption. Permeation of magnesium ascorbyl phosphate was not enhanced by the Er:YAG laser. The CO2 laser at a lower fluence promoted vitamin C permeation with no ablation of the stratum corneum or epidermal layers. Further enhancement was observed with the CO2 laser at higher fluences, which was accompanied by a prominent ablation effect. Microdermabrasion ablated the stratum corneum layers with minimal disruption of the skin barrier properties according to transepidermal water loss levels. The flux and skin deposition of vitamin C across microdermabrasion-treated skin was approximately 20-fold higher than that across intact skin. The techniques used in this study may be useful for basic and clinical investigations of enhancement of topical vitamin C delivery.

Administration, Topical↗
PubMed2002

Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production.

Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is an active constituent of Rheum palmatum, and showed inhibitory activity on lipopolysaccharide-induced NO production in our previous study. However, the apoptosis-inducing activity of emodin has remained undefined. Among three structurally related anthraquinones, including emodin, physcion, and chrysophanol, emodin showed the most potent cytotoxic effects on HL-60 cells, accompanied by the dose- and time-dependent appearance of characteristics of apoptosis including an increase in DNA ladder intensity, morphological changes, appearance of apoptotic bodies, and an increase in hypodiploid cells. Emodin at apoptosis-inducing concentrations causes rapid and transient induction of caspase 3/CPP32 activity, but not caspase 1 activity, according to cleavage of caspase 3 substrates poly(ADP-ribose) polymerase and D4-GDI proteins, the appearance of cleaved caspase 3 fragments being detected in emodin- but not physcion- or chrysophanol-treated HL-60 cells. A decrease in the anti-apoptotic protein, Mcl-1, was detected in emodin-treated HL-60 cells, whereas other Bcl-2 family proteins including Bax, Bcl-2, Bcl-XL, and Bad remained unchanged. The caspase 3 inhibitor, Ac-DEVD-CHO, but not the caspase 1 inhibitor, Ac-YVAD-CHO, attenuated emodin-induced DNA ladders, associated with the blockage of PARP and D4-GDI cleavage. Free radical scavenging agents including NAC, catalase, SOD, ALL, DPI, L-NAME and PDTC showed no preventive effect on emodin-induced apoptotic responses, whereas NAC, CAT and PDTC prevented HL-60 cells from ROS (H(2)O(2))-induced apoptosis through inhibition of caspase 3 cascades. Induction of catalase, but not SOD, activity was detected in emodin-treated HL-60 cells by in gel activity assays, and H(2)O(2)-induced intracellular peroxide level was significantly reduced by prior treatment of emodin in HL-60 cells. Our experiments provide evidence that emodin is an effective apoptosis inducer in HL-60 cells through activation of the caspase 3 cascade, but that it is independent of ROS production.

Apoptosis↗
PubMed2002

In vitro and in vivo inhibitory activities of rutin, wogonin, and quercetin on lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production.

Flavonoids are widely distributed in plants, but their biological functions are still unclear. In the present study, in vitro and in vivo experiments were performed to demonstrate the inhibitory activities of rutin, wogonin, and quercetin on lipopolysaccharide-induced nitric oxide (NO) and prostaglandin E(2) production in RAW 264.7 macrophages, primary peritoneal macrophages, and Balb/c mice, respectively. In vitro results showed that wogonin and quercetin dose-dependently suppressed lipopolysaccharide-induced NO production in RAW 264.7 macrophages and primary peritoneal macrophages without a notable cytotoxic effect on either cell types associated with a decrease in inducible nitric oxide synthase (iNOS) protein expression in both cells. Rutin, at 80 microM only, had a slight but obvious inhibitory effect on lipopolysaccharide-induced NO production in primary peritoneal macrophages. Both wogonin and quercetin attenuated lipopolysaccharide-induced prostaglandin E(2) production in vitro. Intravenous injection of lipopolysaccharide (10 mg/kg, i.v.) resulted in a time-dependent induction of NO production in serum, and pretreatment with the L-arginine analog N-nitro-L-arginine methyl ester (L-NAME) blocked this induction. Intravenous pretreatment of Balb/c mice with rutin, wogonin or quercetin for 1 h followed by lipopolysaccharide treatment significantly inhibited lipopolysaccharide-induced NO production, but no inhibition of prostaglandin E(2) production was found. A decrease in iNOS protein, but not cyclooxygenase-2 protein, was detected in liver and lung specimens of lipopolysaccharide-treated Balb/c mice in the presence of rutin, wogonin or quercetin. In conclusion, data obtained both in vitro and in vivo suggest that wogonin and quercetin exert inhibitory activity on lipopolysaccharide-induced NO production through suppression of iNOS expression.

Animals↗
PubMed2002

Nitric oxide and prostaglandin E2 participate in lipopolysaccharide/interferon-gamma-induced heme oxygenase 1 and prevent RAW264.7 macrophages from UV-irradiation-induced cell death.

Induction of heme oxygenase (HO)-1 during inflammation has been demonstrated in many cell types, but the contribution of inflammatory molecules nitric oxide (NO) and prostaglandin E(2) (PGE(2)) has remained unresolved. Here we show that NO donors including sodium nitroprusside (SNP) and spermine nonoate (SP-NO), and PGE(2) significantly stimulate HO-1 expression in RAW264.7 macrophages, associated with alternative induction on NO and PGE(2) in medium, respectively. NO donors also show the inductive effect on cyclo-oxygenase 2 protein and PGE(2) production. In the presence of lipopolysaccharide and interferon-gamma (LPS/IFN-gamma), HO-1 protein was induced slightly but significantly, and SNP, SP-NO, and PGE(2) enhanced HO-1 protein induced by LPS/IFN-gamma. L-Arginine analogs N-nitro-L-arginine methyl ester (L-NAME) and N-nitro-L-arginine (NLA) significantly block HO-1 protein induced by LPS/IFN-gamma associated with a decrease in NO (not PGE(2)) production. And, NSAIDs aspirin and diclofenase dose dependently inhibited LPS/IFN-gamma-induced HO-1 protein accompanied by suppression of PGE(2) (not NO) production. PD98059 (a specific inhibitor of MEKK), but not SB203580 (a specific inhibitor of p38 kinase), attenuated PGE(2) (not SP-NO) induced HO-1 protein. Under UVC (100 J/m(2)) and UVB (50 J/m(2)) irradiation, PGE(2) or SP-NO treatment prevents cells from UVC or UVB-induced cell death, and HO-1 inhibitor tin protoporphyrin (SnPP) reverses the preventive effects of PGE(2) and SP-NO. The protective activity induced by PGE(2) on UVC or UVB irradiation-induced cell death was blocked by MAPK inhibitor PD98059 (not SB203580). These results demonstrated that inflammatory molecules NO and PGE(2) were potent inducers of HO-1 gene, and protected cells from UV-irradiation-induced cell death through HO-1 induction.

Animals↗