K. Gawron | Jagiellonian University in Krakow (original) (raw)

Papers by K. Gawron

Research paper thumbnail of Role of Nitric Oxide in Physiology and Pathology of the Gastrointestinal Tract

Mini-Reviews in Medicinal Chemistry, 2008

In this paper the physiological role of NO and isoforms of NOS in the gastrointestinal tract and ... more In this paper the physiological role of NO and isoforms of NOS in the gastrointestinal tract and the involvement of NO in pathological processes of digestive tract as well as the perspective of therapeutic use of NO-donating drugs and selective inhibitors of phosphodiesterase in the treatment of gastric diseases were presented.

Research paper thumbnail of Cellular toxicity of oxycholesterols

BioEssays, 2006

Oxycholesterols (OS) are formed from cholesterol or its immediate precursors by enzymatic or free... more Oxycholesterols (OS) are formed from cholesterol or its immediate precursors by enzymatic or free radical action in vivo, or they may be derived from food. OS exhibit a wide spectrum of biological activities. In OS cytotoxicity, several mechanisms seem to be involved: e.g. inhibition of HMG-CoA reductase activity, antiproliferative action, apoptosis induction, replacement of cholesterol by OS in membranes followed by changes in cellular membrane structure and functionality, and immune system functions alteration. Furthermore, OS may be mutagenic and carcinogenic and may serve as intracellular signaling or regulatory molecules. Here we review OS cellular activities with special attention to the cytotoxic action in vivo and in vitro using experimental models.

Research paper thumbnail of Clinical and histo-morphological presentation of isolated maxillo–palatal fibromatosis

Objectives: Presentation of a rare case of isolated maxillo–palatal fibromatosis, modified approa... more Objectives: Presentation of a rare case of isolated maxillo–palatal fibromatosis, modified approach to treatment and one year follow–up. Methods: A 35–year–old male reported to the clinic complaining of overgrowth in upper right maxillo–palatal region of gingiva, bleeding when brushing teeth and with difficulties in keeping oral hygiene. The surgery was modified due to the close to the palatal artery location of the lesion, and comprised internal bevel incision, a partial, wedge–shaped excision of the excessive tissue, mobilization of the flap and suturing. Excised tissue size was 0.7 cm in diameter and 3 cm long. Immediately after surgery, gingival biopsy was fixed in 10% formalin in phosphate buffer saline for 24 h at 4 degrees centigrade, dehydrated, paraffin embedded and serially sectioned. Tissue sections were stained by haematoxylin–eosin and Heidenhain’s trichrome methods followed by histo–morphological evaluation (Nikon Eclipse Ti, Japan). Results: The medical and dental his...

Research paper thumbnail of PGE2–signaling pathway in gingival fibroblasts is modulated by Porphyromonas gingivalis peptidylarginine deiminase (PPAD)

BACKGROUND: Enzymatic deimination (citrullination) of peptidylarginine residues constitutes a com... more BACKGROUND: Enzymatic deimination (citrullination) of peptidylarginine residues constitutes a common mechanism of posttranslational modification affecting structure and function of proteins and peptides. In humans, it is carried out by 5 different peptidylarginine deiminases (PADs). Among prokaryotes only P. gingivalis (Pg), a bacterium strongly associated with pathogenesis of periodontitis, expresses PAD activity. Pg PAD (PPAD) is unique since it citrullinates preferentially C-terminal Arg residues. Due to the combined activity of PPAD and Arg-specific gingipains, Pg is highly citrullinated on its cell surface. Conversely, PPAD very efficiently citrullinates bradykinin (BK), a host peptide with powerful biological activities relevant to the pathogenesis of periodontitis. This includes an effect on prostaglandin E2 (PGE2) synthesis. Therefore, we investigated if PPAD contributes to Pg interaction with primary human gingival fibroblasts (PHGF) and how this interaction affects the PGE...

Research paper thumbnail of Anti-fibrotic potential of a chimeric IgG variant in cell culture established from hereditary gingival fibromatosis with a high propensity for recurrence and immunoreactive component within the lesion

BACKGROUND: Gingival fibromatosis comprises abnormal, progressive, diffuse or localized growth of... more BACKGROUND: Gingival fibromatosis comprises abnormal, progressive, diffuse or localized growth of the gingiva. The condition may hinder oral cavity hygiene and erode underlying bone. The long–term benefits of surgery cannot be predicted while alternative, efficient and non–invasive methods are not available at present. AIM: to test the inhibitory effect of an anti–collagen chimeric IgG variant in the cell culture of gingival fibroblasts taken from a patient with hereditary gingival fibromatosis. MATERIAL AND METHODS: Gingival biopsies collected from the mandible were used for histological study and to establish fibroblast cultures. Tissue sections were stained with haematoxylin –eosin and Heidenhain’s trichrome. By using a collagen–specific Western blot and immunofluorescent staining the inhibitory effect of a chimeric IgG on collagen fibril formation was determined in fibroblast cultures. RESULTS: Histological analysis revealed mild epithelial hyperplasia with singular elongated re...

Research paper thumbnail of Pierwotne komórkowe modele dziąsłowe i ich zastosowanie w badaniach zapalenia przyzębia oraz włókniakowatości dziąseł

Pierwotne modele komórkowe dziąsła stosowane są w badaniach:

Research paper thumbnail of Gingipains as an important virulence factor in development of aspiration pneumonia

Research paper thumbnail of Peptidyl arginine deiminase from porphyromonas gingivalis abolishes anaphylatoxin C5a activity

Evasion of killing by the complement system, a crucial part of innate immunity, is a key evolutio... more Evasion of killing by the complement system, a crucial part of innate immunity, is a key evolutionary strategy of many human pathogens. A major etiological agent of chronic periodontitis, the Gram-negative bacterium Porphyromonas gingivalis, produces a vast arsenal of virulence factors that compromise human defense mechanisms. One of these is peptidylarginine deiminase (PPAD), an enzyme unique to P. gingivalis among bacteria, which converts Arg residues in polypeptide chains into citrulline. Here, we report that PPAD citrullination of a critical C-terminal arginine of the anaphylatoxin C5a disabled the protein function. Treatment of C5a with PPAD in vitro resulted in decreased chemotaxis of human neutrophils and diminished calcium signaling in monocytic cell line U937 transfected with the C5a receptor (C5aR) and loaded with a fluorescent intracellular calcium probe: Fura-2 AM. Moreover, a low degree of citrullination of internal arginine residues by PPAD was also detected using mass spectrometry. Further, after treatment of C5 with outer membrane vesicles naturally shed by P. gingivalis, we observed generation of C5a totally citrullinated at the C-terminal Arg-74 residue (Arg74Cit). In stark contrast, only native C5a was detected after treatment with PPAD-null outer membrane vesicles. Our study suggests reduced antibacterial and proinflammatory capacity of citrullinated C5a, achieved via lower level of chemotactic potential of the modified molecule, and weaker cell activation. In the context of previous studies, which showed crosstalk between C5aR and Toll-like receptors, as well as enhanced arthritis development in mice infected with PPAD-expressing P. gingivalis, our findings support a crucial role of PPAD in the virulence of P. gingivalis.

Research paper thumbnail of Role of Nitric Oxide in Physiology and Pathology of the Gastrointestinal Tract

Mini-Reviews in Medicinal Chemistry, 2008

In this paper the physiological role of NO and isoforms of NOS in the gastrointestinal tract and ... more In this paper the physiological role of NO and isoforms of NOS in the gastrointestinal tract and the involvement of NO in pathological processes of digestive tract as well as the perspective of therapeutic use of NO-donating drugs and selective inhibitors of phosphodiesterase in the treatment of gastric diseases were presented.

Research paper thumbnail of Cellular toxicity of oxycholesterols

BioEssays, 2006

Oxycholesterols (OS) are formed from cholesterol or its immediate precursors by enzymatic or free... more Oxycholesterols (OS) are formed from cholesterol or its immediate precursors by enzymatic or free radical action in vivo, or they may be derived from food. OS exhibit a wide spectrum of biological activities. In OS cytotoxicity, several mechanisms seem to be involved: e.g. inhibition of HMG-CoA reductase activity, antiproliferative action, apoptosis induction, replacement of cholesterol by OS in membranes followed by changes in cellular membrane structure and functionality, and immune system functions alteration. Furthermore, OS may be mutagenic and carcinogenic and may serve as intracellular signaling or regulatory molecules. Here we review OS cellular activities with special attention to the cytotoxic action in vivo and in vitro using experimental models.

Research paper thumbnail of Clinical and histo-morphological presentation of isolated maxillo–palatal fibromatosis

Objectives: Presentation of a rare case of isolated maxillo–palatal fibromatosis, modified approa... more Objectives: Presentation of a rare case of isolated maxillo–palatal fibromatosis, modified approach to treatment and one year follow–up. Methods: A 35–year–old male reported to the clinic complaining of overgrowth in upper right maxillo–palatal region of gingiva, bleeding when brushing teeth and with difficulties in keeping oral hygiene. The surgery was modified due to the close to the palatal artery location of the lesion, and comprised internal bevel incision, a partial, wedge–shaped excision of the excessive tissue, mobilization of the flap and suturing. Excised tissue size was 0.7 cm in diameter and 3 cm long. Immediately after surgery, gingival biopsy was fixed in 10% formalin in phosphate buffer saline for 24 h at 4 degrees centigrade, dehydrated, paraffin embedded and serially sectioned. Tissue sections were stained by haematoxylin–eosin and Heidenhain’s trichrome methods followed by histo–morphological evaluation (Nikon Eclipse Ti, Japan). Results: The medical and dental his...

Research paper thumbnail of PGE2–signaling pathway in gingival fibroblasts is modulated by Porphyromonas gingivalis peptidylarginine deiminase (PPAD)

BACKGROUND: Enzymatic deimination (citrullination) of peptidylarginine residues constitutes a com... more BACKGROUND: Enzymatic deimination (citrullination) of peptidylarginine residues constitutes a common mechanism of posttranslational modification affecting structure and function of proteins and peptides. In humans, it is carried out by 5 different peptidylarginine deiminases (PADs). Among prokaryotes only P. gingivalis (Pg), a bacterium strongly associated with pathogenesis of periodontitis, expresses PAD activity. Pg PAD (PPAD) is unique since it citrullinates preferentially C-terminal Arg residues. Due to the combined activity of PPAD and Arg-specific gingipains, Pg is highly citrullinated on its cell surface. Conversely, PPAD very efficiently citrullinates bradykinin (BK), a host peptide with powerful biological activities relevant to the pathogenesis of periodontitis. This includes an effect on prostaglandin E2 (PGE2) synthesis. Therefore, we investigated if PPAD contributes to Pg interaction with primary human gingival fibroblasts (PHGF) and how this interaction affects the PGE...

Research paper thumbnail of Anti-fibrotic potential of a chimeric IgG variant in cell culture established from hereditary gingival fibromatosis with a high propensity for recurrence and immunoreactive component within the lesion

BACKGROUND: Gingival fibromatosis comprises abnormal, progressive, diffuse or localized growth of... more BACKGROUND: Gingival fibromatosis comprises abnormal, progressive, diffuse or localized growth of the gingiva. The condition may hinder oral cavity hygiene and erode underlying bone. The long–term benefits of surgery cannot be predicted while alternative, efficient and non–invasive methods are not available at present. AIM: to test the inhibitory effect of an anti–collagen chimeric IgG variant in the cell culture of gingival fibroblasts taken from a patient with hereditary gingival fibromatosis. MATERIAL AND METHODS: Gingival biopsies collected from the mandible were used for histological study and to establish fibroblast cultures. Tissue sections were stained with haematoxylin –eosin and Heidenhain’s trichrome. By using a collagen–specific Western blot and immunofluorescent staining the inhibitory effect of a chimeric IgG on collagen fibril formation was determined in fibroblast cultures. RESULTS: Histological analysis revealed mild epithelial hyperplasia with singular elongated re...

Research paper thumbnail of Pierwotne komórkowe modele dziąsłowe i ich zastosowanie w badaniach zapalenia przyzębia oraz włókniakowatości dziąseł

Pierwotne modele komórkowe dziąsła stosowane są w badaniach:

Research paper thumbnail of Gingipains as an important virulence factor in development of aspiration pneumonia

Research paper thumbnail of Peptidyl arginine deiminase from porphyromonas gingivalis abolishes anaphylatoxin C5a activity

Evasion of killing by the complement system, a crucial part of innate immunity, is a key evolutio... more Evasion of killing by the complement system, a crucial part of innate immunity, is a key evolutionary strategy of many human pathogens. A major etiological agent of chronic periodontitis, the Gram-negative bacterium Porphyromonas gingivalis, produces a vast arsenal of virulence factors that compromise human defense mechanisms. One of these is peptidylarginine deiminase (PPAD), an enzyme unique to P. gingivalis among bacteria, which converts Arg residues in polypeptide chains into citrulline. Here, we report that PPAD citrullination of a critical C-terminal arginine of the anaphylatoxin C5a disabled the protein function. Treatment of C5a with PPAD in vitro resulted in decreased chemotaxis of human neutrophils and diminished calcium signaling in monocytic cell line U937 transfected with the C5a receptor (C5aR) and loaded with a fluorescent intracellular calcium probe: Fura-2 AM. Moreover, a low degree of citrullination of internal arginine residues by PPAD was also detected using mass spectrometry. Further, after treatment of C5 with outer membrane vesicles naturally shed by P. gingivalis, we observed generation of C5a totally citrullinated at the C-terminal Arg-74 residue (Arg74Cit). In stark contrast, only native C5a was detected after treatment with PPAD-null outer membrane vesicles. Our study suggests reduced antibacterial and proinflammatory capacity of citrullinated C5a, achieved via lower level of chemotactic potential of the modified molecule, and weaker cell activation. In the context of previous studies, which showed crosstalk between C5aR and Toll-like receptors, as well as enhanced arthritis development in mice infected with PPAD-expressing P. gingivalis, our findings support a crucial role of PPAD in the virulence of P. gingivalis.