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Lamina propria macrophage phenotypes in relation to Escherichia coli in Crohn's disease.

Elliott TR, Rayment NB, Hudspith BN, Hands RE, Taylor K, Parkes GC, Prescott NJ, Petrovska L, Hermon-Taylor J, Brostoff J, Boussioutas A, Mathew CG, Bustin SA, Sanderson JD - BMC Gastroenterol (2015)

Bottom Line: In inflamed tissue, E. coli-unladen macrophages expressed high TNFα, IL-23 & iNOS and lower IL-10 & CD163.In CD, intra-macrophage E. coli are commonly found and LP macrophages express characteristic cytokine mRNA profiles according to E. coli carriage.Persistence of E. coli within LP macrophages may provide a stimulus for chronic inflammation.

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. elliott_timothy@hotmail.com.

ABSTRACT

Background: Abnormal handling of E. coli by lamina propria (LP) macrophages may contribute to Crohn's disease (CD) pathogenesis. We aimed to determine LP macrophage phenotypes in CD, ulcerative colitis (UC) and healthy controls (HC), and in CD, to compare macrophage phenotypes according to E. coli carriage.

Methods: Mucosal biopsies were taken from 35 patients with CD, 9 with UC and 18 HCs. Laser capture microdissection was used to isolate E. coli-laden and unladen LP macrophages from ileal or colonic biopsies. From these macrophages, mRNA was extracted and cytokine and activation marker expression measured using RT-qPCR.

Results: E. coli-laden LP macrophages were identified commonly in mucosal biopsies from CD patients (25/35, 71 %), rarely in UC (1/9, 11 %) and not at all in healthy controls (0/18). LP macrophage cytokine mRNA expression was greater in CD and UC than healthy controls. In CD, E. coli-laden macrophages expressed high IL-10 & CD163 and lower TNFα, IL-23 & iNOS irrespective of macroscopic inflammation. In inflamed tissue, E. coli-unladen macrophages expressed high TNFα, IL-23 & iNOS and lower IL-10 & CD163. In uninflamed tissue, unladen macrophages had low cytokine mRNA expression, closer to that of healthy controls.

Conclusion: In CD, intra-macrophage E. coli are commonly found and LP macrophages express characteristic cytokine mRNA profiles according to E. coli carriage. Persistence of E. coli within LP macrophages may provide a stimulus for chronic inflammation.

No MeSH data available.


Related in: MedlinePlus

E. coli-laden macrophages express a similar phenotype in inflamed and uninflamed tissue high IL-10 (c), CD163 (d), lower TNFα (a) and IL-23 (b). E. coli-unladen macrophages express a proinflammatory phenotype in inflamed tissue high TNFα (a), and IL-23 (b), lower IL-10 (c), CD163 (d) but in uninflamed tissue express cytokine mRNA expression nearer to that of healthy controls (dotted line = healthy control median mRNA expression). MØ = macrophage. *P < .05, **P < .01, ***P < .001. Paired t tests used for within subjects statistical analysis. Presence or absence of inflammation determined by macroscopic appearance at endoscopy
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Fig4: E. coli-laden macrophages express a similar phenotype in inflamed and uninflamed tissue high IL-10 (c), CD163 (d), lower TNFα (a) and IL-23 (b). E. coli-unladen macrophages express a proinflammatory phenotype in inflamed tissue high TNFα (a), and IL-23 (b), lower IL-10 (c), CD163 (d) but in uninflamed tissue express cytokine mRNA expression nearer to that of healthy controls (dotted line = healthy control median mRNA expression). MØ = macrophage. *P < .05, **P < .01, ***P < .001. Paired t tests used for within subjects statistical analysis. Presence or absence of inflammation determined by macroscopic appearance at endoscopy

Mentions: E. coli-laden macrophages expressed a similar phenotype in inflamed and uninflamed mucosa (Fig. 4(a) – (d)). Conversely, E. coli-unladen macrophages from uninflamed mucosa expressed much lower cytokine and surface marker mRNA levels than in inflamed mucosa (for all P < .001 except CD163 P = NS) (Fig. 4(a) – (d)). These were at levels closer to, and in some cases, indistinguishable from controls.Fig. 4


Lamina propria macrophage phenotypes in relation to Escherichia coli in Crohn's disease.

Elliott TR, Rayment NB, Hudspith BN, Hands RE, Taylor K, Parkes GC, Prescott NJ, Petrovska L, Hermon-Taylor J, Brostoff J, Boussioutas A, Mathew CG, Bustin SA, Sanderson JD - BMC Gastroenterol (2015)

E. coli-laden macrophages express a similar phenotype in inflamed and uninflamed tissue high IL-10 (c), CD163 (d), lower TNFα (a) and IL-23 (b). E. coli-unladen macrophages express a proinflammatory phenotype in inflamed tissue high TNFα (a), and IL-23 (b), lower IL-10 (c), CD163 (d) but in uninflamed tissue express cytokine mRNA expression nearer to that of healthy controls (dotted line = healthy control median mRNA expression). MØ = macrophage. *P < .05, **P < .01, ***P < .001. Paired t tests used for within subjects statistical analysis. Presence or absence of inflammation determined by macroscopic appearance at endoscopy
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4490755&req=5

Fig4: E. coli-laden macrophages express a similar phenotype in inflamed and uninflamed tissue high IL-10 (c), CD163 (d), lower TNFα (a) and IL-23 (b). E. coli-unladen macrophages express a proinflammatory phenotype in inflamed tissue high TNFα (a), and IL-23 (b), lower IL-10 (c), CD163 (d) but in uninflamed tissue express cytokine mRNA expression nearer to that of healthy controls (dotted line = healthy control median mRNA expression). MØ = macrophage. *P < .05, **P < .01, ***P < .001. Paired t tests used for within subjects statistical analysis. Presence or absence of inflammation determined by macroscopic appearance at endoscopy
Mentions: E. coli-laden macrophages expressed a similar phenotype in inflamed and uninflamed mucosa (Fig. 4(a) – (d)). Conversely, E. coli-unladen macrophages from uninflamed mucosa expressed much lower cytokine and surface marker mRNA levels than in inflamed mucosa (for all P < .001 except CD163 P = NS) (Fig. 4(a) – (d)). These were at levels closer to, and in some cases, indistinguishable from controls.Fig. 4

Bottom Line: In inflamed tissue, E. coli-unladen macrophages expressed high TNFα, IL-23 & iNOS and lower IL-10 & CD163.In CD, intra-macrophage E. coli are commonly found and LP macrophages express characteristic cytokine mRNA profiles according to E. coli carriage.Persistence of E. coli within LP macrophages may provide a stimulus for chronic inflammation.

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Nutritional Sciences Division, King's College London, Franklin Wilkins Building, 150 Stamford Street, London, SE1 9NH, UK. elliott_timothy@hotmail.com.

ABSTRACT

Background: Abnormal handling of E. coli by lamina propria (LP) macrophages may contribute to Crohn's disease (CD) pathogenesis. We aimed to determine LP macrophage phenotypes in CD, ulcerative colitis (UC) and healthy controls (HC), and in CD, to compare macrophage phenotypes according to E. coli carriage.

Methods: Mucosal biopsies were taken from 35 patients with CD, 9 with UC and 18 HCs. Laser capture microdissection was used to isolate E. coli-laden and unladen LP macrophages from ileal or colonic biopsies. From these macrophages, mRNA was extracted and cytokine and activation marker expression measured using RT-qPCR.

Results: E. coli-laden LP macrophages were identified commonly in mucosal biopsies from CD patients (25/35, 71 %), rarely in UC (1/9, 11 %) and not at all in healthy controls (0/18). LP macrophage cytokine mRNA expression was greater in CD and UC than healthy controls. In CD, E. coli-laden macrophages expressed high IL-10 & CD163 and lower TNFα, IL-23 & iNOS irrespective of macroscopic inflammation. In inflamed tissue, E. coli-unladen macrophages expressed high TNFα, IL-23 & iNOS and lower IL-10 & CD163. In uninflamed tissue, unladen macrophages had low cytokine mRNA expression, closer to that of healthy controls.

Conclusion: In CD, intra-macrophage E. coli are commonly found and LP macrophages express characteristic cytokine mRNA profiles according to E. coli carriage. Persistence of E. coli within LP macrophages may provide a stimulus for chronic inflammation.

No MeSH data available.


Related in: MedlinePlus