Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics

Pace, Elisabetta; Sano, Caterina Di; Ferraro, Maria; Bruno, Andreina; Caputo, Valentina; Gallina, Salvatore; Gjomarkaj, Mark

doi:10.1016/j.pupt.2015.02.003

Cited by 13 publications

(9 citation statements)

References 43 publications

(62 reference statements)

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“…In contrast, some authors have described no differences in the staining for mCD14 37 , 38 , even though these could be the result of a low statistical sample size. Reduced levels of mCD14 or TLR4 in AA makes biological sense 39 , as signal transduction through CD14/TLR4 leads to IL-12 secretion, a powerful inducer of TH 1 polarization 13 . Therefore, attenuated mCD14 levels on antigen presenting cells (APCs) could favour TH 2 -driven allergic asthma 4 , 5 , 13 , 16 .…”

Section: Discussionmentioning

confidence: 99%

The CD14 (−159 C/T) SNP is associated with sCD14 levels and allergic asthma, but not with CD14 expression on monocytes

Nieto‐Fontarigo

Salgado

San-José

et al. 2018

Sci Rep

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LPS-ligation to CD14/TLR-4 on monocytes/macrophages triggers the production of IL-12-family cytokines. IL12/18 promote TH1-differentiation, counteracting the TH2-driven asthma. Therefore, CD14 modulation could alter the TH2-differentiation and should be taken into account when studying asthma. To analyse the alteration in CD14 levels and its association with CD14 (−159 C/T) SNP (rs2569190) in Caucasian adults with stable allergic asthma, we performed a cross-sectional study (277 healthy subjects vs. 277 patients) where clinical parameters, CD14 values and the CD14 (−159 C/T) SNP were studied. Apart from typical biomarkers, we found an increment of neuron-specific enolase (NSE) in allergic asthma, probably linked to monocyte activity. Indeed, we evidenced increased monocyte numbers, but lower CD14 expression and normalised sCD14 values in patients. Moreover, we noticed an association of the T allele (P = 0.0162) and TT genotype (P = 0.0196) of the CD14 SNP with a decreased risk of allergic asthma and augmented sCD14 levels. In conclusion, monocyte CD14 expression and normalized sCD14 values were reduced in stable state asthmatics, and this could be related to the presence of an expanded CD14low monocyte subset. This study also demonstrates that the CD14 (−159 C/T) polymorphism is a risk factor for moderate-severe allergic asthma in adult Caucasians.

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Section: Discussionmentioning

confidence: 99%

The CD14 (−159 C/T) SNP is associated with sCD14 levels and allergic asthma, but not with CD14 expression on monocytes

Nieto‐Fontarigo

Salgado

San-José

et al. 2018

Sci Rep

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“…These effects involved regulatory T lymphocyte (Treg) induction, down-regulation of TLR4 and the potential emergence of a tolerogenic dendritic cell (DC) subset. Moreover, Pace et al demonstrated in 2015 that LPS was significantly able to induce Foxp3 expression in lymphocytes and in total CD4 + CD25 − lymphocytes from asthmatic patients and controls 38 . ENO1 could therefore have immunomodulatory effects via its dual role and these mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Soluble alpha-enolase activates monocytes by CD14-dependent TLR4 signalling pathway and exhibits a dual function

Guillou

Fréret

Fondard

et al. 2016

Sci Rep

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Rheumatoid arthritis (RA) is the most common form of chronic inflammatory rheumatism. Identifying auto-antigens targeted by RA auto-antibodies is of major interest. Alpha-enolase (ENO1) is considered to be a pivotal auto-antigen in early RA but its pathophysiologic role remains unknown. The main objective of this study was to investigate the in vitro effects of soluble ENO1 on peripheral blood mononuclear cells (PBMC) from healthy donors and RA patients in order to determine the potential pathogenic role of ENO1. ELISA, transcriptomic analysis, experiments of receptor inhibition and flow cytometry analysis were performed to determine the effect, the target cell population and the receptor of ENO1. We showed that ENO1 has the ability to induce early production of pro-inflammatory cytokines and chemokines with delayed production of IL-10 and to activate the innate immune system. We demonstrated that ENO1 binds mainly to monocytes and activates the CD14-dependent TLR4 pathway both in healthy subjects and in RA patients. Our results establish for the first time that ENO1 is able to activate in vitro the CD14-dependent TLR4 pathway on monocytes involving a dual mechanism firstly pro-inflammatory and secondly anti-inflammatory. These results contribute to elucidating the role of this auto-antigen in the pathophysiologic mechanisms of RA.

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“…In addition to this finding, after in vitro stimulation with LPS, the production of both TNF- α and IFN- γ in PBMC supernatant was significantly increased by oral corticosteroids [ 75 ]. Similarly, Pace et al [ 76 ] reported that TLR4 and TLR2 expression were increased in Treg lymphocytes from allergic asthmatic subjects after budesonide treatment compared to healthy controls, providing further understanding of the action mechanism of budesonide on the control of inflammation in asthma. Furthermore, an increased level of IL-10 and decreased level of IL-6 and TNF- α were observed after budesonide administration, confirming the modulatory potential of budesonide in immune responses to allergic subjects.…”

Section: Tlrs Targeted Therapeuticsmentioning

confidence: 99%

Holding the Inflammatory System in Check: TLRs and Their Targeted Therapy in Asthma

Dong

Xiong

Zhang

et al. 2016

Mediators of Inflammation

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Inflammation is a complex biological response to detrimental stimuli and can be a double-edged sword. Inflammation plays a protective role in removing pathogenic factors, but dysregulated inflammation is associated with several major fatal diseases such as asthma, cancer, and cardiovascular diseases. Asthma is a complex heterogenous disease caused by genetic and environmental factors. TLRs are the primary proteins associated with the innate and adaptive immune responses to these fatal factors and play an important role in recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), which initiates the downstream immune response. Due to the complex TLRs cascade and nowadays unsuccessful control in asthma, new studies are focused on TLRs and other potential targets in TLR cascade to minimize airway inflammation.

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Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics

Cited by 13 publications

References 43 publications

The CD14 (−159 C/T) SNP is associated with sCD14 levels and allergic asthma, but not with CD14 expression on monocytes

The CD14 (−159 C/T) SNP is associated with sCD14 levels and allergic asthma, but not with CD14 expression on monocytes

Soluble alpha-enolase activates monocytes by CD14-dependent TLR4 signalling pathway and exhibits a dual function

Holding the Inflammatory System in Check: TLRs and Their Targeted Therapy in Asthma

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