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Gustafson-Svärd, Christina
Publications (10 of 23) Show all publications
Christerson, U., Keita, Å. V., Winberg, M. E., Söderholm, J. D. & Gustafson-Svärd, C. (2019). Possible Involvement of Intracellular Calcium-Independent Phospholipase A(2) in the Release of Secretory Phospholipases from Mast Cells-Increased Expression in Ileal Mast Cells of Crohn's Disease. Cells, 8(7), 1-15, Article ID 672.
Open this publication in new window or tab >>Possible Involvement of Intracellular Calcium-Independent Phospholipase A(2) in the Release of Secretory Phospholipases from Mast Cells-Increased Expression in Ileal Mast Cells of Crohn's Disease
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2019 (English)In: Cells, E-ISSN 2073-4409, Vol. 8, no 7, p. 1-15, article id 672Article in journal (Refereed) Published
Abstract [en]

Increased activity of secretory phospholipases A(2) (sPLA(2)) type-II was previously observed in ileum of Crohn's disease (CD). Our aims were to explore the involvement of calcium-independent (i)PLA(2 beta) in the release of sPLA(2)s from the human mast cell (MC) line (HMC-1) and investigate expressions of cytosolic (c)PLA(2) alpha, iPLA(2)beta, sPLA(2)-IIA and sPLA(2)-V in MCs of CD ileum. The release of sPLA(2) was investigated in HMC-1 by immunocytochemistry and ELISA. The expression intensities of PLA(2)s in mucosal MCs, and the proportion of PLA(2)-positive MCs, were investigated in normal ileum and in ileum from patients with CD by immunohistochemistry. The calcium ionophore-stimulated release of sPLA(2)-IIA and sPLA(2)-V from HMC-1 was reduced by the iPLA(2)-inhibitor bromoenol lactone. All four PLA(2)s were detectable in mucosal MCs, both in normal ileum and in CD, but the proportion of iPLA(2)beta-containing mucosal MCs and the expression intensity of sPLA(2)-IIA was increased in CD. Results indicate that iPLA(2)beta is involved in the secretion of sPLA(2)s from HMC-1, and suggest that iPLA(2)beta-mediated release of sPLA(2) from intestinal MCs may contribute to CD pathophysiology. Ex vivo studies on isolated mucosal mast cells are however needed to clarify the precise role of MC PLA(2)s in the inflammatory processes of CD.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
phospholipases A(2), mast cells, Crohn's disease, inflammation
National Category
Cell Biology Cell and Molecular Biology
Research subject
Natural Science, Biomedical Sciences; Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-88801 (URN)10.3390/cells8070672 (DOI)000478902000073 ()31277247 (PubMedID)
Available from: 2019-08-28 Created: 2019-08-28 Last updated: 2019-08-28Bibliographically approved
Christerson, U., Keita, Å. V., Söderholm, J. D. & Gustafson-Svärd, C. (2009). Increased expression of protease-activated receptor-2 in mucosal mast cells in Crohn's ileitis. Paper presented at 13th International Congress of Mucosal Immunology, Tokyo, JAPAN, JUL 09-12, 2007. Journal of Crohn's & Colitis, 3(2), 100-108
Open this publication in new window or tab >>Increased expression of protease-activated receptor-2 in mucosal mast cells in Crohn's ileitis
2009 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 3, no 2, p. 100-108Article in journal (Refereed) Published
Abstract [en]

Background and aims

Activation of protease-activated receptor-2 (PAR-2) may stimulate various events of importance in inflammatory processes, including release of inflammatory mast cell mediators. PAR-2 is frequently up-regulated during inflammatory conditions, but it is not known if the expression is altered in Crohn's disease. The aim of the present study was to investigate the ileal mucosal PAR-2 expression in Crohn's ileitis, with particular emphasis on the expression in ileal mucosal mast cells.

Methods

Surgical specimens from the distal ileum were collected from patients with Crohn's ileitis and patients with colonic cancer as controls. The overall expression of PAR-2 was investigated by Western blot, and the presence of PAR-2 expressing mucosal mast cells by immunohistochemistry and cell counting. The effect of tumor necrosis factor-α (TNF-α) on the PAR-2 expression in a human mast cell line (HMC-1) was investigated by RT-PCR and immunocytochemistry.

Results

In Crohn's specimens, the fraction of PAR-2-expressing mucosal mast cells was increased about 2.5 times (P < 0.001; n = 14) compared with specimens from control patients (n = 6). No difference was found between inflamed (n = 6) and uninflamed Crohn's specimens (P > 0.05; n = 8). Exposure to TNF-α for 48 h up-regulated PAR-2 mRNA and protein expression in the HMC-1 cell line.

Conclusion

PAR-2 is up-regulated on ileal mucosal mast cells in Crohn's ileitis, possibly due to the action of inflammatory cytokines, such as TNF-α. This may contribute to perpetuating the inflammatory process in the intestinal mucosa in Crohn's ileitis.

Keywords
Crohn's ileitis, Mast cells, Protease-activated receptor-2, Tumor necrosis factor-α
National Category
Medical and Health Sciences
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1968 (URN)10.1016/j.crohns.2008.11.003 (DOI)
Conference
13th International Congress of Mucosal Immunology, Tokyo, JAPAN, JUL 09-12, 2007
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2017-12-12Bibliographically approved
Christerson, U., Keita, Å. V., Söderholm, J. D. & Gustafson-Svärd, C. (2009). Potential role of protease-activated receptor-2-stimulated activation of cytosolic phospholipase A2 in intestinal myofibroblast proliferation: Implications for stricture formation in Crohn´s disease. Paper presented at 10th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases, Montreal, CANADA,SEP 16-19, 2007. Journal of Crohn's & Colitis, 3(1), 15-24
Open this publication in new window or tab >>Potential role of protease-activated receptor-2-stimulated activation of cytosolic phospholipase A2 in intestinal myofibroblast proliferation: Implications for stricture formation in Crohn´s disease
2009 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 3, no 1, p. 15-24Article in journal (Refereed) Published
Abstract [en]

Background and aims

Myofibroblast hyperplasia contributes to muscularis mucosae thickening and stricture formation in Crohn's disease (CD). Protease-activated receptor-2 (PAR-2) and cytosolic phospholipase A2 (cPLA2) are known regulators of cell growth, but their significance in intestinal myofibroblast proliferation remain to be elucidated. The principle aims of the present study were to investigate if PAR-2 is expressed in the expanded muscularis mucosa in ileal CD specimens, if inflammatory cytokines may stimulate PAR-2 expression in intestinal myofibroblasts, and if PAR-2 and cPLA2 may regulate intestinal myofibroblast growth.

Methods

Immunohistochemistry was used for detection of PAR-2 in ileal CD specimens. Studies on PAR-2 expression, PLA2 activation and cell growth were performed in a human intestinal myofibroblast cell line, CCD-18Co. PAR-2 expression was investigated by RT-PCR and immunocytochemistry. PLA2 activity was analyzed by quantification of released 14C-arachidonic acid (14C-AA). Cell growth was examined by 3H-thymidine incorporation and cell counting.

Results

The thickened muscularis mucosae of the CD specimens showed strong PAR-2 expression. In cultured myofibroblasts, tumor necrosis factor-α (TNF-α) up-regulated PAR-2 mRNA and protein, and potentiated PAR-2-stimulated 14C-AA release by two known PAR-2 activators, trypsin and SLIGRL-NH2. The release of 14C-AA was dependent on cPLA2. Trypsin stimulated the proliferation of serum-starved cells, and inhibition of cPLA2 reduced normal cell growth and abolished the growth-promoting effect of trypsin.

Conclusions

The results suggest that PAR-2-mediated cPLA2 activation might be of importance in intestinal myofibroblast proliferation. The results also point to the possibility that PAR-2 up-regulation by inflammatory cytokines, like TNF-α, may modulate this effect.

 

 

 

 

 

Keywords
Crohn's disease, Intestinal myofibroblasts, Phospholipase A2, Protease-activated receptor-2, Tumor necrosis factor-α
National Category
Medical and Health Sciences
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1967 (URN)10.1016/j.crohns.2008.10.002 (DOI)
Conference
10th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases, Montreal, CANADA,SEP 16-19, 2007
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2017-12-12Bibliographically approved
Gustafson-Svärd, C., Åkesson Nilsson, G., Mattsson, M., Sundin, P. & Wesén, C. (2001). Removal of xenobiotic dichlorostearic acid from phospholipids and neutral lipids in cultured human cell lines by ß-oxidation and secretion of dichloromyristic acid. Pharmacol & Toxicol, 89, 56-64
Open this publication in new window or tab >>Removal of xenobiotic dichlorostearic acid from phospholipids and neutral lipids in cultured human cell lines by ß-oxidation and secretion of dichloromyristic acid
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2001 (English)In: Pharmacol & Toxicol, Vol. 89, p. 56-64Article in journal (Refereed) Published
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1741 (URN)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2011-09-22Bibliographically approved
Lilja, I., Gustafson-Svärd, C., Franzén, L., Sjödahl, R., Andersen, S. & Johansen, B. (2000). Presence of group IIa secretory phospholipase A2 in mast cells and macrophages in normal human ileal submucosa and in Crohn´s disease. Clin Chem Lab Med, 38, 1231-1236
Open this publication in new window or tab >>Presence of group IIa secretory phospholipase A2 in mast cells and macrophages in normal human ileal submucosa and in Crohn´s disease
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2000 (English)In: Clin Chem Lab Med, Vol. 38, p. 1231-1236Article in journal (Refereed) Published
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1739 (URN)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2011-09-22Bibliographically approved
Lilja, I., Gustafson-Svärd, C., Franzén, L. & Sjödahl, R. (2000). Tumour necrosis factor-α in ileal mast cells in patients with Crohn´s disease. Digestion, 61, 68-76
Open this publication in new window or tab >>Tumour necrosis factor-α in ileal mast cells in patients with Crohn´s disease
2000 (English)In: Digestion, Vol. 61, p. 68-76Article in journal (Refereed) Published
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1738 (URN)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2011-09-22Bibliographically approved
Gustafson-Svärd, C., Lilja, I., Hallböök, O. & Sjödahl, R. (1997). Cyclooxygenase and colon cancer; clues to the aspirin effect?. Ann Med, 29, 247-252
Open this publication in new window or tab >>Cyclooxygenase and colon cancer; clues to the aspirin effect?
1997 (English)In: Ann Med, Vol. 29, p. 247-252Article in journal (Refereed) Published
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1740 (URN)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2011-09-20Bibliographically approved
Gustafson-Svärd, C., Lilja, I., Hallböök, O. & Sjödahl, R. (1996). Cyclooxygenase-1 and cyclooxygenase-2 gene expression in human colorectal adenocarcinomas and in azoxymethane induced colonic tumours in rats. Gut, 38, 79-84
Open this publication in new window or tab >>Cyclooxygenase-1 and cyclooxygenase-2 gene expression in human colorectal adenocarcinomas and in azoxymethane induced colonic tumours in rats
1996 (English)In: Gut, Vol. 38, p. 79-84Article in journal (Refereed) Published
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1737 (URN)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2011-09-16Bibliographically approved
Gustafson-Svärd, C., Sjödahl, R., Lilja, I. & Tagesson, C. (1995). Cytosolic phospholipase A2 and cyclooxygenase-2 mediate release and metabolism of arachidonic acid in tumor necrosis factor-α-primed cultured intestinal epithelial cells (INT 407). Scand J Gastroenterol, 30, 1000-1007
Open this publication in new window or tab >>Cytosolic phospholipase A2 and cyclooxygenase-2 mediate release and metabolism of arachidonic acid in tumor necrosis factor-α-primed cultured intestinal epithelial cells (INT 407)
1995 (English)In: Scand J Gastroenterol, Vol. 30, p. 1000-1007Article in journal (Refereed) Published
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1735 (URN)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2011-09-15Bibliographically approved
Dimberg, J., Lilja, I., Weström, B., Tagesson, C., Söderkvist, P. & Gustafson-Svärd, C. (1995). Ontogeny of group II phospholipase A2 gene expression in rat stomach and ileum. Biol Neonate, 67, 113-121
Open this publication in new window or tab >>Ontogeny of group II phospholipase A2 gene expression in rat stomach and ileum
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1995 (English)In: Biol Neonate, Vol. 67, p. 113-121Article in journal (Refereed) Published
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-1734 (URN)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2011-09-15Bibliographically approved
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