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Disruption of macrophage pro-inflammatory cytokine release in Crohn's disease is associated with reduced optineurin expression in a subset of patients.

Smith AM, Sewell GW, Levine AP, Chew TS, Dunne J, O'Shea NR, Smith PJ, Harrison PJ, Macdonald CM, Bloom SL, Segal AW - Immunology (2015)

Bottom Line: There were no differentially expressed genes identified between the two groups, consistent with genetic heterogeneity; however, a number of molecules were found to be under-expressed in subgroups of CD patients.Reduced OPTN expression coincided with lower intracellular protein levels and diminished cytokine secretion after bacterial stimulation both in the patients and with small interfering RNA knockdown in THP-1 cells.Identifying and studying subgroups of patients with shared defective gene expression could aid our understanding of the mechanisms underlying highly heterogeneous diseases such as CD.

View Article: PubMed Central - PubMed

Affiliation: Microbial Diseases, Eastman Dental Institute, University College London, London, UK.

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Related in: MedlinePlus

Inflammatory cytokine release from monocyte-derived macrophages (MDM) from patients with Crohn's disease (CD; n = 43) and healthy controls (HC; n = 39) after 24 hr heat-killed Escherichia coli clone NCTC 10418 (HkEc) stimulation. (a) Tumour necrosis factor (TNF), (b) interferon-γ (IFN-γ), (c) interleukin-6 (IL-6), (d) IL-8, and (e) IL-10. Graphical representation of the regression analysis performed using a Pearson's correlation on the cytokine secretion from MDM after 24 hr HkEc stimulation in both the (f) HC (n = 39) and (g) CD (n = 43) cohorts. Increased thickness of the interconnecting lines demonstrates the strength of the association (r value) and the colour denotes the direction (blue = positive and red = negative). *P < 0·05, **P < 0·01 and ***P < 0·001.
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fig01: Inflammatory cytokine release from monocyte-derived macrophages (MDM) from patients with Crohn's disease (CD; n = 43) and healthy controls (HC; n = 39) after 24 hr heat-killed Escherichia coli clone NCTC 10418 (HkEc) stimulation. (a) Tumour necrosis factor (TNF), (b) interferon-γ (IFN-γ), (c) interleukin-6 (IL-6), (d) IL-8, and (e) IL-10. Graphical representation of the regression analysis performed using a Pearson's correlation on the cytokine secretion from MDM after 24 hr HkEc stimulation in both the (f) HC (n = 39) and (g) CD (n = 43) cohorts. Increased thickness of the interconnecting lines demonstrates the strength of the association (r value) and the colour denotes the direction (blue = positive and red = negative). *P < 0·05, **P < 0·01 and ***P < 0·001.

Mentions: Given the important roles of TNF-α, IFN-γ, IL-6, IL-8 and IL-10 in acute inflammation and the previous association of these cytokines with CD, we determined their secretion by macrophages over a 24-hr period of stimulation with HkEc. The secretion of TNF-α (P = 0·0045) and IFN-γ (P = 0·0004) were significantly lower in the CD cohort (n = 43) compared with the HC (n = 39) (Fig.1a,b) whereas equivalent amounts of IL-6, IL-8 and IL-10 were released in the two groups (Fig.1c–e).


Disruption of macrophage pro-inflammatory cytokine release in Crohn's disease is associated with reduced optineurin expression in a subset of patients.

Smith AM, Sewell GW, Levine AP, Chew TS, Dunne J, O'Shea NR, Smith PJ, Harrison PJ, Macdonald CM, Bloom SL, Segal AW - Immunology (2015)

Inflammatory cytokine release from monocyte-derived macrophages (MDM) from patients with Crohn's disease (CD; n = 43) and healthy controls (HC; n = 39) after 24 hr heat-killed Escherichia coli clone NCTC 10418 (HkEc) stimulation. (a) Tumour necrosis factor (TNF), (b) interferon-γ (IFN-γ), (c) interleukin-6 (IL-6), (d) IL-8, and (e) IL-10. Graphical representation of the regression analysis performed using a Pearson's correlation on the cytokine secretion from MDM after 24 hr HkEc stimulation in both the (f) HC (n = 39) and (g) CD (n = 43) cohorts. Increased thickness of the interconnecting lines demonstrates the strength of the association (r value) and the colour denotes the direction (blue = positive and red = negative). *P < 0·05, **P < 0·01 and ***P < 0·001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4264909&req=5

fig01: Inflammatory cytokine release from monocyte-derived macrophages (MDM) from patients with Crohn's disease (CD; n = 43) and healthy controls (HC; n = 39) after 24 hr heat-killed Escherichia coli clone NCTC 10418 (HkEc) stimulation. (a) Tumour necrosis factor (TNF), (b) interferon-γ (IFN-γ), (c) interleukin-6 (IL-6), (d) IL-8, and (e) IL-10. Graphical representation of the regression analysis performed using a Pearson's correlation on the cytokine secretion from MDM after 24 hr HkEc stimulation in both the (f) HC (n = 39) and (g) CD (n = 43) cohorts. Increased thickness of the interconnecting lines demonstrates the strength of the association (r value) and the colour denotes the direction (blue = positive and red = negative). *P < 0·05, **P < 0·01 and ***P < 0·001.
Mentions: Given the important roles of TNF-α, IFN-γ, IL-6, IL-8 and IL-10 in acute inflammation and the previous association of these cytokines with CD, we determined their secretion by macrophages over a 24-hr period of stimulation with HkEc. The secretion of TNF-α (P = 0·0045) and IFN-γ (P = 0·0004) were significantly lower in the CD cohort (n = 43) compared with the HC (n = 39) (Fig.1a,b) whereas equivalent amounts of IL-6, IL-8 and IL-10 were released in the two groups (Fig.1c–e).

Bottom Line: There were no differentially expressed genes identified between the two groups, consistent with genetic heterogeneity; however, a number of molecules were found to be under-expressed in subgroups of CD patients.Reduced OPTN expression coincided with lower intracellular protein levels and diminished cytokine secretion after bacterial stimulation both in the patients and with small interfering RNA knockdown in THP-1 cells.Identifying and studying subgroups of patients with shared defective gene expression could aid our understanding of the mechanisms underlying highly heterogeneous diseases such as CD.

View Article: PubMed Central - PubMed

Affiliation: Microbial Diseases, Eastman Dental Institute, University College London, London, UK.

Show MeSH
Related in: MedlinePlus