It is becoming increasingly clear that the inflammatory reaction can be ascribed to a complex array of mediators generated and released from activated phagocytes. In this study, the effect of PAF on interleukin-1(IL-1) activity by rat alveolar macrophages(AM) was examined using thymocyte proliferation assay in the supernate of sample obtained after 24 hr culture. When AM were cultured with PAF alone, no change in IL-1 activity was observed. However, the combined addition of PAF and muramyl dipeptide(MDP) or lipopolysaccharide(LPS) to AM cultures markedly enhanced IL-1 activity by 2-3 fold compared with AM cultures with the stimulant alone in a concentration dependent fashion. The peak effect was found at 10-8 M PAF with MDP and 10-14 M PAF with LPS. the effect of PAF was also tested in silica, toxic respirable dust, -added AM cultures as well as in the cultures containing bacterial compounds. Although silica did not stimulate the IL-1 activity, PAF could enhance IL-1 activity by 2 fold above the value of the silica-treated AM cultures with the peak response at 10-2 M PAF. Optimal enhancement of IL-1 activity occurred when MDP and PAF were present together at the initiation of the 24 hr AM cultures. Additionally, the biologically inactive precursor/metabolite of PAF, lyso-PAF failed to induce enhancement of IL-1 activity. When the specific, but structurally different PAF receptor antagonists, BN 5202 (10-5 M) and CV 3988(10-5M) was treated 15 min before addition of PAF(10-8 M) and MDP(10 microgram/ml) to the AM cultures, it markedly inhibited the enhancement of IL-1 activity induced by PAF. The effects of these PAF antagonists were also observed in LPS(1.0 microgram/ml)-stimulated cells. Collectively, these data suggest that PAF enhances IL-1 activity by interaction with a specific receptor.
Animals ; Dust ; Interleukin-1* ; Macrophages, Alveolar* ; Phagocytes ; Rats ; Silicon Dioxide ; Thymocytes

This investigation is to determine whether the surface complexation of iron influence acute pulmonary responses induced by silica. For this study, three varieties of cation complexed silica were used: silica-H+, -Zn2+, and -Fe3+, since the first two are not active in the transport of electrons and generate little free radicals relative to the dust with the surface iron. Rats (270 to 280 g) were intratracheally (IT) instilled with saline, silica-H+, -Zn2+, or -Fe3+ (5 mg in 0.5 ml saline). After 4 h, cell number, type, and differentiation were analysed in the bronchoalveolar lavage cells, and the levels of lactate dehydrogenase (LDH) and total protein were determined in the lavage fluid. In addition, bronchoalveolar lavage cells were cultured, and nitric oxide production was measured using nitrate assay. Inducible nitric oxide synthase (iNOS) mRNA in the bronchoalveolar lavage cells was also determined by northern blot analysis. Differential counts of the lavage cells showed that red blood cells were increased by 9-, 8-, and 13-fold and total leukocytes (lymphocytes plus polymorphonuclear neutrophils) by 48-, 36-, and 33-fold, following IT silica- H+, -Zn2+, and -Fe3+, respectively compared with the saline group. Meanwhile, there were no significant differences in red blood cells and total leukocytes among any of the cation complexed silica groups. The levels of LDH and total protein in the lavage fluid were significantly increased by 3- to 4-fold. However, compared among these silica groups, Fe3+ complexation did not significantly change the LDH activity and total protein. NO production in cultured bronchoalveolar lavage cells was elevated by 2-fold, following IT any of the silica treatments compared with the saline group. Furthermore, the steady-state levels of iNOS mRNA in the lavage cells were greatly increased. There were any differences in iNOS mRNA expression among the silica-treated groups as with NO production. These findings suggest that surface complexed iron may not influence the acute pulmonary responses resulted from 4h exposure to silica.
Animals ; Blotting, Northern ; Bronchoalveolar Lavage ; Cell Count ; Dust ; Erythrocytes ; Free Radicals ; Iron ; L-Lactate Dehydrogenase ; Leukocytes ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Rats ; RNA, Messenger ; Silicon Dioxide* ; Therapeutic Irrigation

Stimulated alveolar macrophages and neutrophils produce nitric oxide, a free radical by an inducible nitric oxide synthase (iNOS), which reacts with superoxide anion to form peroxynitrite, a more highly reactive toxic species. The objectives of the present study were to evaluate acute inflammatory lung injury and to determine iNOS mRNA induction and nitric oxide production by rat broncho-alveolar lavage cells following intratracheal treatment of silica. After 4 h exposure to silica, differential counts of bronchoalveolar lavage cells and lactate dehydrogenase (LDH) activity as well as total protein in the broncho-alveolar lavage fluid were determined. Broncho-alveolar lavage cells were also assayed for iNOS mRNA and the productions of nitrite and nitrate measured in the cells cultured. Differential analysis of broncho-alveolar lavage cells showed that the number of alveolar macrophages slightly decreased following silica treatment; however, red blood cells, lymphocytes, and neutrophils significantly were increased by 9-, 14-, and 119-fold following silica treatment, respectively, compared with the saline control. It was also found significant increases in the LDH activity and total protein in the lavage fluid obtained from silica-treated rats, indicating silica-induced acute lung injury. Northern blot analysis demonstrated that the steady state levels of iNOS mRNA in broncho-alveolar lavage cells were increased following silica treatment. The productions of nitrite and nitrate in the cultured cells were significantly increased by 2-fold following silica treatment, respectively, which were attenuated by the NOS inhibitor Nomega-nitro-L-arginine-methyl ester(L-NAME) and partially reversed by L-arginine. These findings suggest that nitric oxide production in alveolar macrophages and recruited neutrophils is increased in response to silica. Nitric oxide may contribute in part to acute inflammatory lung injury.
Acute Lung Injury ; Animals ; Arginine ; Blotting, Northern ; Bronchoalveolar Lavage ; Cells, Cultured ; Erythrocytes ; L-Lactate Dehydrogenase ; Lung Injury* ; Lung* ; Lymphocytes ; Macrophages, Alveolar ; Neutrophils ; Nitric Oxide Synthase Type II* ; Nitric Oxide* ; Peroxynitrous Acid ; Rats ; RNA, Messenger* ; Silicon Dioxide ; Superoxides ; Therapeutic Irrigation

Platelet-activating factor (PAF) enhanced interleukin-1 (IL-1) activity by the interaction with a specific receptor in rat alveolar macrophages. In this study, we investigated the role of endogenous arachidonate metabolites and intracellular calcium mobilization in the PAF-induced IL-1 activity. Alveolar macrophages were preincubated with 5-lipoxygenase and cyclooxygenase inhibitors 30 min before the addition of PAF and lipopolysaccharide (LPS). After 24 h culture, IL-1 activity was measured in the supernate of sample using the thymocyte proliferation assay. Inhibition of 5-lipoxygenase by nordihydroguaiaretic acid and AA-861 completely blocked the PAF-induced enhancement of IL-1 activity with IC50 of 2 micrometer and 5 micrometer, respectively. In contrast, the inhibition of cyclooxygenase pathway by indomethacin and ibuprofen resulted in the potentiation in PAF-induced IL-1 activity with maximal effect at 1 micrometer and 5 micrometer, respectively. In addition, leukotriene B4 and prostaglandin E2 production were observed in PAF-stimulated alveolar macrophage culture. As could be expected, 5-lipoxygenase and cyclooxygenase inhibitors abolished PAFstimulated leukotriene B4 and prostaglandin E2 production, respectively. The effects of PAF on intracellular calcium mobilization in alveolar macrophages were evaluated using the calcium-sensitive dye fura-2 at the single cell level. PAF at any dose between 10-16 and 10-8M did not increase intracellular calcium. Furthermore, there was no effective change of intracellular calcium level when PAF was added to alveolar macrophages in the presence of LPS or LPS + LTB4, and 4, 24 and 48h after treatment of these stimulants. Together, the results indicate that IL-1 activity induced by PAF is differently regulated through subsequent induction of endogenous 5-lpoxygenase and cyclooxygenase pathways, but not dependent on calcium signalling pathway.
Animals ; Arachidonate 5-Lipoxygenase ; Calcium ; Cyclooxygenase Inhibitors ; Dinoprostone ; Fura-2 ; Ibuprofen ; Indomethacin ; Inhibitory Concentration 50 ; Interleukin-1* ; Leukotriene B4 ; Lipoxygenase Inhibitors ; Macrophages, Alveolar* ; Masoprocol ; Prostaglandin-Endoperoxide Synthases ; Rats ; Thymocytes

Recent evidence supports a neuroprotective role of Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) against ischemic brain injury. However, the molecular mechanisms of SHP-2 activation and those governing how SHP-2 exerts its function under oxidative stress conditions are not well understood. Recently we have reported that reactive oxygen species (ROS)-mediated oxidative stress promotes the phosphorylation of endogenous SHP-2 through lipid rafts, and that this phosphorylation strongly occurs in astrocytes, but not in microglia. To investigate the molecules involved in events leading to phosphorylation of SHP-2, raft proteins were analyzed using astrocytes and microglia. Interestingly, caveolin-1 and -2 were detected only in astrocytes but not in microglia, whereas flotillin-1 was expressed in both cell types. To examine whether the H2O2-dependent phosphorylation of SHP-2 is mediated by caveolin-1, we used specific small interfering RNA (siRNA) to downregulate caveolin-1 expression. In the presence of caveolin-1 siRNA, the level of SHP-2 phosphorylation induced by H2O2 was significantly decreased, compared with in the presence of control siRNA. Overexpression of caveolin-1 effectively increased H2O2-induced SHP-2 phosphorylation in microglia. Lastly, H2O2 induced extracellular signal-regulated kinase (ERK) activation in astrocytes through caveolin-1. Our results suggest that caveolin-1 is involved in astrocyte-specific intracellular responses linked to the SHP-2-mediated signaling cascade following ROS-induced oxidative stress.
Animals ; Astrocytes/*metabolism ; Caveolin 1/*genetics/metabolism ; Caveolin 2/genetics ; Cell Line ; Cells, Cultured ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression ; Humans ; Microglia/metabolism ; Phosphoric Monoester Hydrolases/*metabolism ; Phosphorylation ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/*metabolism ; Rats ; Reactive Oxygen Species/*metabolism

Purpose: Fractional microneedle radiofrequency (FMR) systems are used to treat inflammatory acne and scarring. Nonetheless, few controlled studies have combined this treatment with the traditional ablative fractional laser (AFL). We aimed to assess the safety and efficacy of the combination of FMR and AFL versus AFL alone in treating acne and acne scars. Materials and Methods: In this 20-week, randomized, split-face study, 23 Korean patients with facial acne and acne scars underwent FMR and AFL treatments. One half of each patient’s face was randomly assigned to receive FMR+AFL, whereas the other half received AFL alone. Treatments were administered in three consecutive sessions at 4-week intervals. This study investigated the severity of inflammatory acne, acne scars, individual lesion counts, depressed scar volumes, as well as patient and physician satisfaction. In addition, five patients underwent skin biopsy, and sebum output was measured. Results: The FMR+AFL treatment demonstrated superior efficacy compared to AFL alone in terms of inflammatory acne and acne scar grading, lesion counts, and subjective satisfaction. The side effects were minimal and well-tolerated in both groups. Immunohistochemical findings from skin biopsy samples revealed that the application of FMR+AFL could induce an inhibitory effect on sebum secretion at the molecular level. Conclusion FMR combined with AFL is a well-tolerated and effective treatment modality for inflammatory acne and acne scarring.

Objectives: This study aims to evaluate the risk assessments of coronavirus 2019 (COVID-19) in the KoreaCenters for Disease Control and Prevention (KCDC), from the point of detection to the provision of basicinformation to the relevant public health authorities. Methods: To estimate the overall risk of specific public health events, probability, and impact at thecountry-level were evaluated using available information. To determine the probability of particularpublic health events, the risk of importation and risk of transmission were taken into consideration.KCDC used 5 levels (“very low,” “low,” “moderate,” “high,” and “very high”) for each category and overallrisk was eventually decided. Results: A total of 8 risk assessments were performed on 8 separate occasions between January 8th toFebruary 28th, 2020, depending on the detection and report of COVID-19 cases in other countries. Theoverall risk of the situation in each assessment increased in severity over this period: “low” (first),“moderate” (second), “high” (third), “high” (fourth), “high” (fifth), “high” (sixth), “high” (seventh), and“very high” (eighth). Conclusion The KCDC’s 8 risk assessments were utilized to activate national emergency responsemechanisms and eventually prepare for the pandemic to ensure the containment and mitigation ofCOVID-19 with non-pharmaceutical public health measures.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder with an incidence of approximately 1 in 5,000 to 10,000 live births. TSC has various clinical manifestations such as multiple hamartomas in systemic organs, including the skin. Angiofibromas are the most common skin lesions in patients with TSC. Although benign, angiofibromas develop in childhood and puberty, and can be psychosocially disfiguring for patients. Skin lesions in TSC, specifically angiofibromas, have no significant risk of malignant transformation after puberty; thus, they require no treatment if not prominent. However, the presentation of TSC is important owing to its impact on patient cosmesis. Surgical treatment and laser therapy are the mainstream treatments for angiofibromas. Although the evidence is limited, topical mammalian target of rapamycin inhibitors such as sirolimus (rapamycin) are effective in facial angiofibroma treatment. We describe an adult patient with an angiofibroma who had an excellent response to treatment with topical rapamycin after a single session of carbon dioxide (CO₂) laser ablation. The patient showed no sign of relapse or recurring lesions for a year. CO₂ laser ablation may serve as a new paradigm of treatment for angiofibromas in TSC. Since the selection of laser devices can be limited for some institutions, we suggest a rather basic but highly effective approach for angiofibroma treatment that can be generally applied with the classic CO₂ device.
Adolescent ; Adult ; Angiofibroma ; Carbon Dioxide ; Hamartoma ; Humans ; Incidence ; Laser Therapy ; Live Birth ; Methods ; Neurocutaneous Syndromes ; Puberty ; Recurrence ; Sirolimus ; Skin ; Tuberous Sclerosis

En coup de sabre variant of linear morphea (LM) is a rare sclerotic skin disorder characterized by disfiguring linear depression of the frontal or frontoparietal forehead. Current attempts for cosmetic correction of atrophic lesions must be preceded by an evaluation of disease activity of LM, either by a sufficient clinical assessment or histologic evidence. Corrective procedures including corrective surgery, autologous fat grafting, hyaluronic acid filler injections were performed with varying degrees of success; still, there is a need for treatment options with non-invasive and long-term maintenance effects. Herein we report the use of micronized acellular dermal matrix filler as a novel and successful treatment for the atrophic defect of LM in a 24-year-old female. Molecular characteristics of the micronized acellular dermal matrix filler give enhanced durability and prolonged volume consistency, which results in a long-term extracellular matrix remodeling effect.

En coup de sabre variant of linear morphea (LM) is a rare sclerotic skin disorder characterized by disfiguring linear depression of the frontal or frontoparietal forehead. Current attempts for cosmetic correction of atrophic lesions must be preceded by an evaluation of disease activity of LM, either by a sufficient clinical assessment or histologic evidence. Corrective procedures including corrective surgery, autologous fat grafting, hyaluronic acid filler injections were performed with varying degrees of success; still, there is a need for treatment options with non-invasive and long-term maintenance effects. Herein we report the use of micronized acellular dermal matrix filler as a novel and successful treatment for the atrophic defect of LM in a 24-year-old female. Molecular characteristics of the micronized acellular dermal matrix filler give enhanced durability and prolonged volume consistency, which results in a long-term extracellular matrix remodeling effect.