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Christerson, Ulrika
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Publications (5 of 5) 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
Magnusson, C., Svensson, A., Christersson, U. & Tågerud, S. (2005). Denervation-induced alterations in gene expression in mouse skeletal muscle. European journal of neuroscience, 21 (2), 577-580
Open this publication in new window or tab >>Denervation-induced alterations in gene expression in mouse skeletal muscle
2005 (English)In: European journal of neuroscience, Vol. 21 (2), p. 577-580Article in journal (Refereed) Published
Research subject
Biomedical Sciences, Pharmacology; Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-684 (URN)
Available from: 2010-04-01 Created: 2010-04-01 Last updated: 2011-09-29Bibliographically approved
Christerson, U., Söderholm, J. & Gustafson-Svärd, C.Cytosolic phospholipase A2 and activity upon stimulation with A23187, trypsin and TNF-2 (cPLA2) and calcium-independent2 (iPLA2) in the human mast cell line HMC-1.
Open this publication in new window or tab >>Cytosolic phospholipase A2 and activity upon stimulation with A23187, trypsin and TNF-2 (cPLA2) and calcium-independent2 (iPLA2) in the human mast cell line HMC-1
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background

 

 
: Mast cells (MC) are considered to be involved in the pathogenesis of Crohn´s disease (CD). A key regulatory event in the production of eicosanoids in MC is the mobilization of arachidonic acid (AA) by the action of phospholipases A2 (PLA2s). The expression of protease activated receptor-2 (PAR-2) is increased on intestinal mast cells in CD, but it is not known if this receptor may influence the PLA2 activity in MC. Although extensively studied in rodent mast cells, not much is known about the PLA2s in human mast cells. The principle aims of the present study were to investigate if the cell line HMC-1 could serve as a model for studies on cytosolic PLA2 (cPLA2) and calcium-independent PLA2 (iPLA2) in human mast cells, and if stimulation of PAR-2 may influence the activity of the two enzymes. Methods: A human mast cell line, HMC-1, was used for the studies. PLA2 activity was analyzed by quantification of radiolabeled fatty acids. PLA2 expression was investigated by RT-PCR and immunocytochemistry. Results: A23187 and the PAR-2-activator trypsin induced a fatty acid release that was not restricted to AA. Only the A23187-induced AArelease was reduced by a combined cPLA2 and iPLA2 inhibitor and by a specific iPLA2 inhibitor. The protein expression of cPLA2, as determined by immunocytochemistry, was very low compared to the expression of iPLA2. TNF-α specifically increased the cPLA2 mRNA expression but had no effect on the protein expression of the PLA2s, as determined by immunocytochemistry. Conclusions: Stimulation with a calcium ionophore may activate iPLA2-dependent AA release, but neither cPLA2 nor iPLA2 seems to be involved in PAR-2-stimulated AA release. TNF-α stimulates cPLA2 mRNA expression, but does not influence the immunocytochemically detected protein level. The expression of cPLA2 and iPLA2 in HMC-1 cells, together with its ability to release radiolabeled fatty acids upon stimulation, makes this cell line a promising model for further studies on cPLA2 and iPLA2 in human MCs. 

National Category
Natural Sciences
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-6509 (URN)
Available from: 2010-06-24 Created: 2010-06-24 Last updated: 2010-10-14Bibliographically approved
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