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Dysregulation of anti-inflammatory annexin A1 expression in progressive Crohns Disease.

Sena A, Grishina I, Thai A, Goulart L, Macal M, Fenton A, Li J, Prindiville T, Oliani SM, Dandekar S, Goulart L, Sankaran-Walters S - PLoS ONE (2013)

Bottom Line: Current IBD therapy utilizes a combination of immunomodulators and biologics to suppress pro-inflammatory effectors of IBD.We found that the reduction in ANXA1 protein levels in plasma coincided with a decrease in the ANXA1 mRNA expression in peripheral blood of IBD patients.ANXA1 expression is upregulated during IFX therapy in patients with a successful intervention but not in clinical non-responders.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology and Immunology, University of California Davis, Davis, California, United States of America ; Nanobiotechnology Laboratory, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil.

ABSTRACT

Background: Development of inflammatory bowel disease (IBD) involves the interplay of environmental and genetic factors with the host immune system. Mechanisms contributing to immune dysregulation in IBD are not fully defined. Development of novel therapeutic strategies is focused on controlling aberrant immune response in IBD. Current IBD therapy utilizes a combination of immunomodulators and biologics to suppress pro-inflammatory effectors of IBD. However, the role of immunomodulatory factors such as annexin A1 (ANXA1) is not well understood. The goal of this study was to examine the association between ANXA1 and IBD, and the effects of anti-TNF-α, Infliximab (IFX), therapy on ANXA1 expression.

Methods: ANXA1 and TNF-α transcript levels in PBMC were measured by RT PCR. Clinical follow up included the administration of serial ibdQs. ANXA1 expression in the gut mucosa was measured by IHC. Plasma ANXA1 levels were measured by ELISA.

Results: We found that the reduction in ANXA1 protein levels in plasma coincided with a decrease in the ANXA1 mRNA expression in peripheral blood of IBD patients. ANXA1 expression is upregulated during IFX therapy in patients with a successful intervention but not in clinical non-responders. The IFX therapy also modified the cellular immune activation in the peripheral blood of IBD patients. Decreased expression of ANXA1 was detected in the colonic mucosa of IBD patients with incomplete resolution of inflammation during continuous therapy, which correlated with increased levels of TNF-α transcripts. Gut mucosal epithelial barrier disruption was evident by increased plasma bacterial 16S levels.

Conclusion: Loss of ANXA1 expression may support inflammation during IBD and can serve as a biomarker of disease progression. Changes in ANXA1 levels may be predictive of therapeutic efficacy.

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Related in: MedlinePlus

ANXA1 is expressed at lower levels in blood of IBD patients.(A) The level of ANXA1 mRNA was determined by real-time RT-PCR analysis from peripheral blood mononuclear cells was lower in IBD patients compared to healthy controls. (B) Plasma Annexin A1 levels were assayed using ELISA. Patients with IBD had lower levels of plasma ANXA1 compared to IBD negative controls. (C) Plasma CRP levels were measured by ELISA. Healthy controls had significantly lower levels of plasma CRP compared to patients with IBD. An inverse correlation was observed between plasma CRP and plasma ANXA1 (D). (*p < 0.05).
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pone-0076969-g002: ANXA1 is expressed at lower levels in blood of IBD patients.(A) The level of ANXA1 mRNA was determined by real-time RT-PCR analysis from peripheral blood mononuclear cells was lower in IBD patients compared to healthy controls. (B) Plasma Annexin A1 levels were assayed using ELISA. Patients with IBD had lower levels of plasma ANXA1 compared to IBD negative controls. (C) Plasma CRP levels were measured by ELISA. Healthy controls had significantly lower levels of plasma CRP compared to patients with IBD. An inverse correlation was observed between plasma CRP and plasma ANXA1 (D). (*p < 0.05).

Mentions: Measurement of ANXA1 gene expression in PBMC from patient groups showed that ANXA1 mRNA levels were significantly lower among IBD patients in comparison to healthy non-IBD controls (p<.05) (Figure 2A). The ANXA1 mRNA levels in PBMCs from IBD patients ranged from 2 to 500 fold lower than that of healthy controls. ANXA1 is generally attached to the plasma membrane and a fraction is shed in the plasma. We measured ANXA1 levels in plasma of IBD patients and healthy controls using ELISA. A previous study reported on decreased ANXA1 levels in plasma of patients with obesity [36]. We found a significantly lower level of free ANXA1 in plasma of IBD patients compared to healthy controls (unpaired T test, P<0.05) (Figure 2B). In contrast, a prominent marker of inflammation, plasma CRP, levels were significantly higher in patients with IBD compared to healthy controls (Figure 2C). A significant negative correlation was found between plasma CRP and plasma ANXA1 levels indicating that reduced levels of ANXA1 were associated with higher levels of inflammation (r2=0.2158; p=0.0294) (Figure 2D).


Dysregulation of anti-inflammatory annexin A1 expression in progressive Crohns Disease.

Sena A, Grishina I, Thai A, Goulart L, Macal M, Fenton A, Li J, Prindiville T, Oliani SM, Dandekar S, Goulart L, Sankaran-Walters S - PLoS ONE (2013)

ANXA1 is expressed at lower levels in blood of IBD patients.(A) The level of ANXA1 mRNA was determined by real-time RT-PCR analysis from peripheral blood mononuclear cells was lower in IBD patients compared to healthy controls. (B) Plasma Annexin A1 levels were assayed using ELISA. Patients with IBD had lower levels of plasma ANXA1 compared to IBD negative controls. (C) Plasma CRP levels were measured by ELISA. Healthy controls had significantly lower levels of plasma CRP compared to patients with IBD. An inverse correlation was observed between plasma CRP and plasma ANXA1 (D). (*p < 0.05).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3794972&req=5

pone-0076969-g002: ANXA1 is expressed at lower levels in blood of IBD patients.(A) The level of ANXA1 mRNA was determined by real-time RT-PCR analysis from peripheral blood mononuclear cells was lower in IBD patients compared to healthy controls. (B) Plasma Annexin A1 levels were assayed using ELISA. Patients with IBD had lower levels of plasma ANXA1 compared to IBD negative controls. (C) Plasma CRP levels were measured by ELISA. Healthy controls had significantly lower levels of plasma CRP compared to patients with IBD. An inverse correlation was observed between plasma CRP and plasma ANXA1 (D). (*p < 0.05).
Mentions: Measurement of ANXA1 gene expression in PBMC from patient groups showed that ANXA1 mRNA levels were significantly lower among IBD patients in comparison to healthy non-IBD controls (p<.05) (Figure 2A). The ANXA1 mRNA levels in PBMCs from IBD patients ranged from 2 to 500 fold lower than that of healthy controls. ANXA1 is generally attached to the plasma membrane and a fraction is shed in the plasma. We measured ANXA1 levels in plasma of IBD patients and healthy controls using ELISA. A previous study reported on decreased ANXA1 levels in plasma of patients with obesity [36]. We found a significantly lower level of free ANXA1 in plasma of IBD patients compared to healthy controls (unpaired T test, P<0.05) (Figure 2B). In contrast, a prominent marker of inflammation, plasma CRP, levels were significantly higher in patients with IBD compared to healthy controls (Figure 2C). A significant negative correlation was found between plasma CRP and plasma ANXA1 levels indicating that reduced levels of ANXA1 were associated with higher levels of inflammation (r2=0.2158; p=0.0294) (Figure 2D).

Bottom Line: Current IBD therapy utilizes a combination of immunomodulators and biologics to suppress pro-inflammatory effectors of IBD.We found that the reduction in ANXA1 protein levels in plasma coincided with a decrease in the ANXA1 mRNA expression in peripheral blood of IBD patients.ANXA1 expression is upregulated during IFX therapy in patients with a successful intervention but not in clinical non-responders.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology and Immunology, University of California Davis, Davis, California, United States of America ; Nanobiotechnology Laboratory, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil.

ABSTRACT

Background: Development of inflammatory bowel disease (IBD) involves the interplay of environmental and genetic factors with the host immune system. Mechanisms contributing to immune dysregulation in IBD are not fully defined. Development of novel therapeutic strategies is focused on controlling aberrant immune response in IBD. Current IBD therapy utilizes a combination of immunomodulators and biologics to suppress pro-inflammatory effectors of IBD. However, the role of immunomodulatory factors such as annexin A1 (ANXA1) is not well understood. The goal of this study was to examine the association between ANXA1 and IBD, and the effects of anti-TNF-α, Infliximab (IFX), therapy on ANXA1 expression.

Methods: ANXA1 and TNF-α transcript levels in PBMC were measured by RT PCR. Clinical follow up included the administration of serial ibdQs. ANXA1 expression in the gut mucosa was measured by IHC. Plasma ANXA1 levels were measured by ELISA.

Results: We found that the reduction in ANXA1 protein levels in plasma coincided with a decrease in the ANXA1 mRNA expression in peripheral blood of IBD patients. ANXA1 expression is upregulated during IFX therapy in patients with a successful intervention but not in clinical non-responders. The IFX therapy also modified the cellular immune activation in the peripheral blood of IBD patients. Decreased expression of ANXA1 was detected in the colonic mucosa of IBD patients with incomplete resolution of inflammation during continuous therapy, which correlated with increased levels of TNF-α transcripts. Gut mucosal epithelial barrier disruption was evident by increased plasma bacterial 16S levels.

Conclusion: Loss of ANXA1 expression may support inflammation during IBD and can serve as a biomarker of disease progression. Changes in ANXA1 levels may be predictive of therapeutic efficacy.

Show MeSH
Related in: MedlinePlus