Clarithromycin inhibits overproduction of muc5ac core protein in murine model of diffuse panbronchiolitis

2003 ◽  
Vol 285 (4) ◽  
pp. L847-L853 ◽  
Author(s):  
Yukihiro Kaneko ◽  
Katsunori Yanagihara ◽  
Masafumi Seki ◽  
Misuzu Kuroki ◽  
Yoshitsugu Miyazaki ◽  
...  
Keyword(s):  
Core Protein ◽  
Periodic Acid ◽  
Protein A ◽  
Mitogen Activated Protein Kinase ◽  
Periodic Acid Schiff ◽  
Western Blots ◽  
Diffuse Panbronchiolitis ◽  
Mucin Production ◽  
Long Term Treatment

Long-term treatment of macrolide antibiotics is considered an effective treatment for diffuse panbronchiolitis (DPB). Although hypersecretion is a common feature of this disease, and it is known that macrolides inhibit mucin production, the mechanism of the effect on mucin production is unclear. The aim of our study was to determine the production of muc5ac core protein, a major core protein of mucin in airway secretion, and the effect of clarithromycin treatment on such production in a mouse model mimicking DPB. Alcian blue-periodic acid-Schiff-positive cells were detected in the lungs of Pseudomonas aeruginosa-infected mice. Western blots of these mice showed muc5ac glycoprotein at day 1 and increased progressively from day 4 to day 14 after inoculation of bacteria. Clarithromycin (10 mg · kg-1· day-1for 7 days) significantly reduced the muc5ac expression at both the mRNA and protein levels. To investigate the role of molecules upstream in muc5ac regulation, we examined the role of mitogen-activated protein kinase. Extracellular signal-regulated kinase 1/2 phosphorylation increased in the infected lung and decreased after treatment. Our results suggest that overproduction of muc5ac plays an important role in the pathogenesis of DPB and that clinical improvement following macrolide therapy seems to involve, at least in part, its inhibition of mucin overproduction, through modulation of intracellular signal transduction.

scholarly journals Activation and activity of glycosylated KLKs 3, 4 and 11

2018 ◽  
Vol 399 (9) ◽  
pp. 1009-1022 ◽  
Author(s):  
Shihui Guo ◽  
Peter Briza ◽  
Viktor Magdolen ◽  
Hans Brandstetter ◽  
Peter Goettig
Keyword(s):  
Physiological Function ◽  
Periodic Acid ◽  
Hek293 Cells ◽  
Secretory Expression ◽  
Detailed Characterization ◽  
Periodic Acid Schiff ◽  
Clinical Biomarkers ◽  
Schiff Reaction

Abstract Human kallikrein-related peptidases 3, 4, 11, and KLK2, the activator of KLK3/PSA, belong to the prostatic group of the KLKs, whose major physiological function is semen liquefaction during the fertilization process. Notably, these KLKs are upregulated in prostate cancer and are used as clinical biomarkers or have been proposed as therapeutic targets. However, this potential awaits a detailed characterization of these proteases. In order to study glycosylated prostatic KLKs resembling the natural proteases, we used Leishmania (LEXSY) and HEK293 cells for secretory expression. Both systems allowed the subsequent purification of soluble pro-KLK zymogens with correct propeptides and of the mature forms. Periodic acid-Schiff reaction, enzymatic deglycosylation assays, and mass spectrometry confirmed the glycosylation of these KLKs. Activation of glycosylated pro-KLKs 4 and 11 turned out to be most efficient by glycosylated KLK2 and KLK4, respectively. By comparing the glycosylated prostatic KLKs with their non-glycosylated counterparts from Escherichia coli, it was observed that the N-glycans stabilize the KLK proteases and change their activation profiles and their enzymatic activity to some extent. The functional role of glycosylation in prostate-specific KLKs could pave the way to a deeper understanding of their biology and to medical applications.

scholarly journals Azithromycin Inhibits MUC5AC Production Induced by the Pseudomonas aeruginosa Autoinducer N-(3-Oxododecanoyl) Homoserine Lactone in NCI-H292 Cells

2004 ◽  
Vol 48 (9) ◽  
pp. 3457-3461 ◽  
Author(s):  
Yoshifumi Imamura ◽  
Katsunori Yanagihara ◽  
Yohei Mizuta ◽  
Masafumi Seki ◽  
Hideaki Ohno ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Bacterial Infection ◽  
Core Protein ◽  
Homoserine Lactone ◽  
Signal Molecule ◽  
Diffuse Panbronchiolitis ◽  
Mucin Production ◽  
Protein Levels ◽  
Extracellular Signal

ABSTRACT The features of chronic airway diseases, including chronic bronchitis, cystic fibrosis, bronchiectasis, and diffuse panbronchiolitis, include chronic bacterial infection and airway obstruction by mucus. Pseudomonas aeruginosa is one of the most common pathogens in chronic lung infection, and quorum-sensing systems contribute to the pathogenesis of this disease. The quorum-sensing signal molecule [N-(3-oxododecanoyl) homoserine lactone (3O-C12-HSL)] not only regulates bacterial virulence but also is associated with the immune response. In this study, we investigated whether 3O-C12-HSL could stimulate the production of a major mucin core protein, MUC5AC. The effect of a macrolide on MUC5AC production was also studied. 3O-C12-HSL induced NCI-H292 cells to express MUC5AC at both the mRNA and the protein levels in time- and dose-dependent manners. A 15-membered macrolide, azithromycin, inhibited MUC5AC production that was activated by 3O-C12-HSL. 3O-C12-HSL induced extracellular signal-regulated kinase (ERK) 1/2 and I-κB phosphorylation in cells, and this induction was suppressed by azithromycin. 3O-C12-HSL-induced MUC5AC production was blocked by the ERK pathway inhibitor PD98059. Our findings suggest that the P. aeruginosa autoinducer 3O-C12-HSL contributes to excessive mucin production in chronic bacterial infection. Azithromycin seems to reduce this mucin production by interfering with intracellular signal transduction.

scholarly journals Loss of NHE8 expression impairs intestinal mucosal integrity

2015 ◽  
Vol 309 (11) ◽  
pp. G855-G864 ◽  
Author(s):  
Aiping Wang ◽  
Jing Li ◽  
Yang Zhao ◽  
Malin E. V. Johansson ◽  
Hua Xu ◽  
...  
Keyword(s):  
Periodic Acid ◽  
Paneth Cell ◽  
Distal Colon ◽  
Goblet Cells ◽  
Paneth Cells ◽  
Wild Type ◽  
Periodic Acid Schiff ◽  
Mucin Production ◽  
Mucosal Integrity ◽  
Mucin 2

The newest member of the Na+/H+ exchanger (NHE) family, NHE8, is abundantly expressed at the apical membrane of the intestinal epithelia. We previously reported that mucin 2 expression was significantly decreased in the colon in NHE8−/− mice, suggesting that NHE8 is involved in intestinal mucosal protection. In this study, we further evaluated the role of NHE8 in intestinal epithelial protection after dextran sodium sulfate (DSS) challenge. Compared with wild-type mice, NHE8−/− mice have increased bacterial adhesion and inflammation, especially in the distal colon. NHE8−/− mice are also susceptible to DSS treatment. Real-time PCR detected a remarkable increase in the expression of IL-1β, IL-6, TNF-α, and IL-4 in DSS-treated NHE8−/− mice compared with DSS-treated wild-type littermates. Immunohistochemistry showed a disorganized epithelial layer in the colon of NHE8−/− mice. Periodic acid-Schiff staining showed a reduction in the number of mature goblet cells and the area of the goblet cell theca in NHE8−/− mice. Phyloxine/tartrazine staining revealed a decrease in functional Paneth cell population in the NHE8−/− small intestinal crypt. The expression of enteric defensins was also decreased in NHE8−/− mice. The reduced mucin production in goblet cells and antimicrobial peptides production in Paneth cells lead to disruption of the intestinal mucosa protection. Therefore, NHE8 may be involved in the establishment of intestinal mucosal integrity by regulating the functions of goblet and Paneth cells.

scholarly journals CD8+CD103+ iTregs inhibit the progression of lupus nephritis by attenuating glomerular endothelial cell injury

Rheumatology ◽  
2019 ◽  
Vol 58 (11) ◽  
pp. 2039-2050 ◽  
Author(s):  
Weijuan Deng ◽  
Minwen Xu ◽  
Qiaoyun Meng ◽  
Zhi Li ◽  
Xiaonan Qiu ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Lupus Nephritis ◽  
Inflammatory Mediators ◽  
Cell Injury ◽  
Periodic Acid ◽  
Treg Cells ◽  
Healthy Controls ◽  
Glomerular Endothelial Cell ◽  
Periodic Acid Schiff

Abstract Objectives We previously reported that ex vivo TGF-β and IL-2–induced CD8+CD103+ regulatory T cells (CD8+CD103+ iTregs) displayed similar immunosuppressive effect and therapeutic function on lupus mice nephritis to that of CD4+Foxp3+ Tregs. In view of the important role of glomerular endothelial cell (GEC) injury in inflammatory processes in SLE, this study aimed to investigate the nature and mechanism of CD8+CD103+ iTregs–mediated amelioration of LN by attenuating GEC injury. Methods Treg cells from patients with SLE and from healthy controls were characterized by flow cytometry analysis. The expression of pro-inflammatory mediators and VEGF were analysed in healthy controls, patients with SLE and MRL/lpr mice by ELISA, western blot, and real-time quantitative RT-PCR (qRT-PCR). Typical lesions of diffuse proliferative LN were observed in MRL/lpr mice through the use of haematoxylin and eosin, Masson, periodic acid–Schiff, periodic acid–Schiff methenamine, transmission electron microscopy and IF microscopy. Angiogenesis was analysed in GECs by cell investigating proliferation, migration, and tube formation. Results The results revealed that the frequency of Treg cells was inversely correlated with the expression of VCAM-1 and ICAM-1 in patients with SLE. Furthermore, adoptive transfer of CD8+CD103+ iTregs to MRL/lpr mice was associated with decreased levels of autoantibodies and proteinuria, reduced renal pathological lesions, and lowered renal deposition of IgG/C3. We further found that CD8+CD103+ iTregs not only suppressed the expression of pro-inflammatory mediators but also attenuated GEC injury by promoting angiogenesis. Conclusion Our study has identified the role of CD8+CD103+ iTregs on attenuating GEC injury and provided a possible application of this new iTregs subset in lupus nephritis and other autoimmune diseases.

scholarly journals Endoplasmic Reticulum Chaperon Tauroursodeoxycholic Acid Attenuates Aldosterone-Infused Renal Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Honglei Guo ◽  
Hongmei Li ◽  
Lilu Ling ◽  
Yong Gu ◽  
Wei Ding
Keyword(s):  
Endoplasmic Reticulum ◽  
Inflammatory Response ◽  
Er Stress ◽  
Renal Injury ◽  
Periodic Acid ◽  
Periodic Acid Schiff ◽  
Tauroursodeoxycholic Acid ◽  
Receive Treatment ◽  
Inflammatory Molecules

Aldosterone (Aldo) is critically involved in the development of renal injury via the production of reactive oxygen species and inflammation. Endoplasmic reticulum (ER) stress is also evoked in Aldo-induced renal injury. In the present study, we investigated the role of ER stress in inflammation-mediated renal injury in Aldo-infused mice. C57BL/6J mice were randomized to receive treatment for 4 weeks as follows: vehicle infusion, Aldo infusion, vehicle infusion plus tauroursodeoxycholic acid (TUDCA), and Aldo infusion plus TUDCA. The effect of TUDCA on the Aldo-infused inflammatory response and renal injury was investigated using periodic acid-Schiff staining, real-time PCR, Western blot, and ELISA. We demonstrate that Aldo leads to impaired renal function and inhibition of ER stress via TUDCA attenuates renal fibrosis. This was indicated by decreased collagen I, collagen IV, fibronectin, and TGF-β expression, as well as the downregulation of the expression of Nlrp3 inflammasome markers, Nlrp3, ASC, IL-1β, and IL-18. This paper presents an important role for ER stress on the renal inflammatory response to Aldo. Additionally, the inhibition of ER stress by TUDCA negatively regulates the levels of these inflammatory molecules in the context of Aldo.

scholarly journals Clinico-pathological study of 273 cases of rhinosporidiosis over a period of ten years in a tertiary care institute catering predominantly rural population of tribal origin

2015 ◽  
Vol 14 (2) ◽  
pp. 159-164 ◽  
Author(s):  
Sanjay Sengupta ◽  
Subrata Pal ◽  
Biplab Kr Biswas ◽  
Sritanu Jana ◽  
Sudhanya Biswas ◽  
...  
Keyword(s):  
Periodic Acid ◽  
Tertiary Care ◽  
Medical Science ◽  
Clinical History ◽  
Periodic Acid Schiff ◽  
Diagnostic Role ◽  
Detailed Clinical History ◽  
And Gender ◽  
Mass Lesions

Introduction: Rhinosporidiosis is a chronic granulomatous infection caused by Rhinosporidium seeberi, an organism whose taxonomy is still debated. The present study was aimed to document the clinico-pathological presentation of rhinosporidiosis in different parts in reference to caste, age and gender. Evaluation of diagnostic role of cytology in the diagnosis of rhinosporidiosis was also explored.Materials and Methods: All histology confirmed rhinosporidial cases were included in the study. Detailed clinical history and examination findings including previous hematological and cytological reports, if available, were collected and tabulated. Periodic Acid Schiff (PAS) and Mucicarmine stains were used over cyto- and histological slides, if necessary.Observations: Male cases were more frequent in these series though this sex difference is less pronounced among tribal population. Majority of the cases belonged to 21-40 years age group. Nose and nasopharynx was the commonest site of infection and polypoid mass lesions were the commonest presentation. Both scrape and aspiration cytology could successfully detect rhinosporidiosis in 100% cases.Discussion: Most of the cases are among poor-socioeconomic status and probably out-door activities and pond bathing habit. Haematological data correlation did not revealed any significant association. Histology is the preferred method for confirmed diagnosis of rhinosporidiosis. Rare cases of misdiagnosis can be avoided by use of special stains.Conclusion: Rhinosporidiosis commonly presents as polypoidal lesions in nose and extra-nasal sites. Histopathology is the standard method for confirmation of diagnosis. Cytology can be used as an adjunct for pre-operative diagnosis of extra-nasal rhinosporidiosis. We recommended use of special stains for diagnosis of difficult cases.Bangladesh Journal of Medical Science Vol.14(2) 2015 p.159-164

SMP-534 inhibits TGF-β-induced ECM production in fibroblast cells and reduces mesangial matrix accumulation in experimental glomerulonephritis

2005 ◽  
Vol 289 (5) ◽  
pp. F998-F1004 ◽  
Author(s):  
Eiji Sugaru ◽  
Mutsuko Sakai ◽  
Kazuhiko Horigome ◽  
Teruhisa Tokunaga ◽  
Makoto Kitoh ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Periodic Acid ◽  
Transforming Growth Factor Β ◽  
Mitogen Activated Protein Kinase ◽  
Cortical Region ◽  
Fibroblast Cells ◽  
Periodic Acid Schiff ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Transforming growth factor-β (TGF-β) is a potent fibrotic factor responsible for the synthesis of extracellular matrix (ECM) and is implicated as the major determinant in pathogenesis of chronic fibroses, including kidney. The novel small compound SMP-534 reduced ECM production induced by TGF-β in fibroblast cells. SMP-534 inhibited TGF-β-induced p38 mitogen-activated protein kinase (p38) activation but did not inhibit epidermal growth factor (EGF)-induced extracellular signal-related kinase (ERK) activation. We also found that oral administration of SMP-534 dose dependently lowered hydroxyproline contents in the cortical region of the kidney in rat anti-Thy-1 nephritis models. In periodic acid-Schiff staining of kidney sections, ECM accumulation was reduced by SMP-534 treatment. These data indicate that SMP-534 has potential in therapy for fibrotic diseases, including nephropathy.

Cells with affinity for periodic acid – Schiff are present in the pars intermedia of Atlantic salmon

1991 ◽  
Vol 69 (12) ◽  
pp. 3105-3108 ◽  
Author(s):  
Martin P. Komourdjian ◽  
Richard L. Saunders
Keyword(s):  
Atlantic Salmon ◽  
Periodic Acid ◽  
Cell Types ◽  
Point Of View ◽  
Pars Intermedia ◽  
Periodic Acid Schiff ◽  
Distinct Cell ◽  
Two Populations ◽  
Evolutionary Point

Examination of pituitaries from two populations of Atlantic salmon (Salmo salar) parr held under natural photoperiods revealed at least two histologically distinct cell types. One type has fine granules with affinity for lead hematoxylin (PIPbH). Another type, hitherto believed to be absent in salmonids, has larger granules which are Schiff-positive (PIPAS). These cells are significantly (P < 0.05) shorter and narrower and have significantly smaller nuclei (P < 0.05) than the PIPbH type. No evidence was found for ascribing to the PIPAS cells the functions assigned to them in other species: melanophore control and reproduction. However, PIPAS granules became evident only during fall-winter, when the smolting process begins. The incidence of these cells rose and then declined sharply during this period, suggesting a possible role in some aspect of smoltification. While the role of these PIPAS cells deserves further study, their presence is in itself important from an evolutionary point of view.

scholarly journals Isolation and some structural analyses of a proteodermatan sulphate from calf skin

1983 ◽  
Vol 213 (2) ◽  
pp. 289-296 ◽  
Author(s):  
T Nakamura ◽  
E Matsunaga ◽  
H Shinkai
Keyword(s):  
Core Protein ◽  
Gradient Centrifugation ◽  
Cetylpyridinium Chloride ◽  
Periodic Acid ◽  
Molar Ratio ◽  
Gel Chromatography ◽  
Dermatan Sulphate ◽  
Periodic Acid Schiff ◽  
Cscl Density Gradient ◽  
Calf Skin

A proteodermatan sulphate was isolated from 0.15 M-NaCl and 0.45 M-NaCl extracts of newborn-calf skin. The proteoglycan was separated from collagen and hyaluronic acid by precipitation with cetylpyridinium chloride and CsCl-density-gradient centrifugation. Further purification was performed by ion-exchange, affinity and molecular-sieve chromatography. The proteoglycan bound to concanavalin A-Sepharose in 1 M-NaCl. It gave a positive reaction with periodic acid/Schiff reagent and contained 8.3% of uronic acid. The dermatan sulphate, the only glycosaminoglycan component, was composed of 74% iduronosylhexosamine units and 26% glucuronosylhexosamine units. The Mr was assessed to be 15000-20000 by gel chromatography. The core protein was found to be a sialoglycoprotein that had O-glycosidic oligosaccharides with N-acetylgalactosamine at the reducing termini. The molar ratio of oligosaccharide chains to dermatan sulphate was approx. 3:1. From these results the proposed structure of proteodermatan sulphate is: one dermatan sulphate chain (average Mr 17500), three O-glycosidic oligosaccharide chains and probably N-glycosidic oligosaccharide chain(s) bound to one core-protein molecule (Mr 55000).

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