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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

Cytokine and surface marker mRNA levels in healthy controls, CD patients with E. coli laden macrophages, CD patients without E. coli laden macrophages and UC patients. Fig. 3(a) From left to right: Healthy controls (n = 18); LP macrophages have low TNFα mRNA expression. Inflamed mucosal biopsies from CD patients with both E. coli-laden and unladen macrophages present (n = 25); E. coli-unladen macrophages had higher mean TNFα mRNA expression (P < .001) than E. coli-laden macrophages. CD patients without E. coli-laden macrophages (n = 10); TNFα mRNA expression of E. coli-unladen macrophages were lower than in E. coli-unladen macrophages from the 25 CD patients in whom both E. coli-laden and unladen were present (P < .001). UC patients (n = 9); E. coli-unladen LP macrophages showed elevated TNFα mRNA levels. Fig 3(b) to (f): Expression of other proinflammatory cytokines (IL-23, IL-6, IL-8) and iNOS is similar to the pattern of TNFα expression in samples from each subject group. Fig. 3 (g) Expression of COX2 is similar to the pattern of TNFα in each group but is lower in UC than in CD. In distinction to the pattern of TNFα expression, Fg. 3 (g) and 3(h) demonstrate that IL-10 and CD-163 mRNA expression are higher in E. coli-laden than E. coli-unladen macrophages in CD (for each; P < .001). *P < .05, **P < .01, ***P < .001. Comparisons of means made with one-way ANOVA and Games-Howell post-hoc pair-wise comparisons. There was no UC data for IL-23 or IL-10. Only one UC patient had E. coli-laden macrophages (cytokine data not shown)
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Fig3: Cytokine and surface marker mRNA levels in healthy controls, CD patients with E. coli laden macrophages, CD patients without E. coli laden macrophages and UC patients. Fig. 3(a) From left to right: Healthy controls (n = 18); LP macrophages have low TNFα mRNA expression. Inflamed mucosal biopsies from CD patients with both E. coli-laden and unladen macrophages present (n = 25); E. coli-unladen macrophages had higher mean TNFα mRNA expression (P < .001) than E. coli-laden macrophages. CD patients without E. coli-laden macrophages (n = 10); TNFα mRNA expression of E. coli-unladen macrophages were lower than in E. coli-unladen macrophages from the 25 CD patients in whom both E. coli-laden and unladen were present (P < .001). UC patients (n = 9); E. coli-unladen LP macrophages showed elevated TNFα mRNA levels. Fig 3(b) to (f): Expression of other proinflammatory cytokines (IL-23, IL-6, IL-8) and iNOS is similar to the pattern of TNFα expression in samples from each subject group. Fig. 3 (g) Expression of COX2 is similar to the pattern of TNFα in each group but is lower in UC than in CD. In distinction to the pattern of TNFα expression, Fg. 3 (g) and 3(h) demonstrate that IL-10 and CD-163 mRNA expression are higher in E. coli-laden than E. coli-unladen macrophages in CD (for each; P < .001). *P < .05, **P < .01, ***P < .001. Comparisons of means made with one-way ANOVA and Games-Howell post-hoc pair-wise comparisons. There was no UC data for IL-23 or IL-10. Only one UC patient had E. coli-laden macrophages (cytokine data not shown)

Mentions: Mean mRNA expression of most cytokines and surface markers (TNFα, IL-23, IL-6, IL-8 & IL-10, iNOS & COX2 (P < .001 for each)) was lower in LP macrophages from healthy controls than from E. coli-laden or unladen macrophages from inflamed CD mucosa (Fig. 3(a) to (g)). Mean CD163 mRNA expression in LP macrophages from healthy controls was not significantly different to E. coli-unladen macrophages (P = .173) but lower than E. coli-laden CD macrophages (P < .001) (Fig. 3(h)).Fig. 3


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)

Cytokine and surface marker mRNA levels in healthy controls, CD patients with E. coli laden macrophages, CD patients without E. coli laden macrophages and UC patients. Fig. 3(a) From left to right: Healthy controls (n = 18); LP macrophages have low TNFα mRNA expression. Inflamed mucosal biopsies from CD patients with both E. coli-laden and unladen macrophages present (n = 25); E. coli-unladen macrophages had higher mean TNFα mRNA expression (P < .001) than E. coli-laden macrophages. CD patients without E. coli-laden macrophages (n = 10); TNFα mRNA expression of E. coli-unladen macrophages were lower than in E. coli-unladen macrophages from the 25 CD patients in whom both E. coli-laden and unladen were present (P < .001). UC patients (n = 9); E. coli-unladen LP macrophages showed elevated TNFα mRNA levels. Fig 3(b) to (f): Expression of other proinflammatory cytokines (IL-23, IL-6, IL-8) and iNOS is similar to the pattern of TNFα expression in samples from each subject group. Fig. 3 (g) Expression of COX2 is similar to the pattern of TNFα in each group but is lower in UC than in CD. In distinction to the pattern of TNFα expression, Fg. 3 (g) and 3(h) demonstrate that IL-10 and CD-163 mRNA expression are higher in E. coli-laden than E. coli-unladen macrophages in CD (for each; P < .001). *P < .05, **P < .01, ***P < .001. Comparisons of means made with one-way ANOVA and Games-Howell post-hoc pair-wise comparisons. There was no UC data for IL-23 or IL-10. Only one UC patient had E. coli-laden macrophages (cytokine data not shown)
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Related In: Results  -  Collection

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Fig3: Cytokine and surface marker mRNA levels in healthy controls, CD patients with E. coli laden macrophages, CD patients without E. coli laden macrophages and UC patients. Fig. 3(a) From left to right: Healthy controls (n = 18); LP macrophages have low TNFα mRNA expression. Inflamed mucosal biopsies from CD patients with both E. coli-laden and unladen macrophages present (n = 25); E. coli-unladen macrophages had higher mean TNFα mRNA expression (P < .001) than E. coli-laden macrophages. CD patients without E. coli-laden macrophages (n = 10); TNFα mRNA expression of E. coli-unladen macrophages were lower than in E. coli-unladen macrophages from the 25 CD patients in whom both E. coli-laden and unladen were present (P < .001). UC patients (n = 9); E. coli-unladen LP macrophages showed elevated TNFα mRNA levels. Fig 3(b) to (f): Expression of other proinflammatory cytokines (IL-23, IL-6, IL-8) and iNOS is similar to the pattern of TNFα expression in samples from each subject group. Fig. 3 (g) Expression of COX2 is similar to the pattern of TNFα in each group but is lower in UC than in CD. In distinction to the pattern of TNFα expression, Fg. 3 (g) and 3(h) demonstrate that IL-10 and CD-163 mRNA expression are higher in E. coli-laden than E. coli-unladen macrophages in CD (for each; P < .001). *P < .05, **P < .01, ***P < .001. Comparisons of means made with one-way ANOVA and Games-Howell post-hoc pair-wise comparisons. There was no UC data for IL-23 or IL-10. Only one UC patient had E. coli-laden macrophages (cytokine data not shown)
Mentions: Mean mRNA expression of most cytokines and surface markers (TNFα, IL-23, IL-6, IL-8 & IL-10, iNOS & COX2 (P < .001 for each)) was lower in LP macrophages from healthy controls than from E. coli-laden or unladen macrophages from inflamed CD mucosa (Fig. 3(a) to (g)). Mean CD163 mRNA expression in LP macrophages from healthy controls was not significantly different to E. coli-unladen macrophages (P = .173) but lower than E. coli-laden CD macrophages (P < .001) (Fig. 3(h)).Fig. 3

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