scholarly journals Intrarenal Toll-like receptor 4 and Toll-like receptor 2 expression correlates with injury in antineutrophil cytoplasmic antibody-associated vasculitis

2018 ◽  
Vol 315 (5) ◽  
pp. F1283-F1294 ◽  
Author(s):  
Kim M. O’Sullivan ◽  
Sharon L. Ford ◽  
Anthony Longano ◽  
A. Richard Kitching ◽  
Stephen R. Holdsworth
Keyword(s):  
Renal Injury ◽  
Estimated Glomerular Filtration Rate ◽  
High Mobility ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Tlr2 Expression ◽  
Toll Like Receptor 4 ◽  
Toll Like Receptor 2 ◽  
Functional Relevance

In antineutrophil cytoplasmic antibody-associated vasculitis (AAV), Toll-like receptors (TLRs) may be engaged by infection-associated patterns and by endogenous danger signals, linking infection and innate inflammation with this autoimmune disease. This study examined intrarenal TLR2, TLR4, and TLR9 expression and renal injury in AAV, testing the hypothesis that increased TLR expression correlates with renal injury. Patients with AAV exhibited both glomerular and tubulointerstitial expression of TLR2, TLR4, and TLR9, with TLR4 being the most prominent in both compartments. Glomerular TLR4 expression correlated with glomerular segmental necrosis and cellular crescents, with TLR2 expression correlating with glomerular segmental necrosis. The extent and intensity of glomerular and tubulointerstitial TLR4 expression and the intensity of glomerular TLR2 expression inversely correlated with the presenting estimated glomerular filtration rate. Although myeloid cells within the kidney expressed TLR2, TLR4, and TLR9, TLR2 and TLR4 colocalized with endothelial cells and podocytes, whereas TLR9 was expressed predominantly by podocytes. The functional relevance of intrarenal TLR expression was further supported by the colocalization of TLRs with their endogenous ligands high-mobility group box 1 and fibrinogen. Therefore, in AAV, the extent of intrarenal TLR4 and TLR2 expression and their correlation with renal injury indicates that TLR4, and to a lesser degree TLR2, may be potential therapeutic targets in this disease.

scholarly journals P1764EXPRESSION OF TOLL-LIKE RECEPTOR 4, BUT NOT THE TOLL-LIKE RECEPTOR 2, MAY BE USEFUL I ASSESING THE RISK OF RENAL TRANSPLANT DETERIORATION IN RECIPIENTS WHO HAVE RECOVERED FROM CYTOMEGALOVIRUS INFECTION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sławomir Zmonarski ◽  
Mirosław Banasik ◽  
Tomasz Gołębiowski ◽  
Letachowicz Krzysztof ◽  
Joanna Zmonarska ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Cmv Infection ◽  
Toll Like Receptor 4 ◽  
Peripheral Blood Mononuclear ◽  
Data Binding ◽  
Toll Like Receptor 2 ◽  
The Impact

Abstract Background and Aims Data binding the expression of Toll-like (TLR) 4 receptor (TLR4ex), or TLR2 receptor (TLR2ex) and transplanted kidney (KT) function and symptomatic infections with CMV (CMV+) and are scarcely available. Objective: To investigate the relationships between TLR4ex and TLR2ex, a relapse of CMV+ and transplant function. Method Materials and methods: TLR4ex and TLR2ex were measured in peripheral blood mononuclear cells of KT recipients. We compared TLR4ex and TLR2ex among 25 CMV+ patients; 81 patients without CMV infection (CMVn). At the beginning (Day-0) TLR4ex, as well as concentrations of cyclosporin A (CyA) and tacrolimus (TAC) were determined. Both CMV+ and CMVn patients were divided according to the respective median of TLR4ex into groups of low-TLR2/4 expression (L-TLR2/4ex) and high-TLR2/4 expression (H-TLR2/4ex). Glomerular filtration rate (EGFR) was assessed on Day-0 and after the follow-up (F-up). The magnitudes of EGFR change (ΔEGFR) were evaluated. Stable treatment along the F-up period (median 11.9 months) was applied. Results Results. In CMV+ TLR2ex of 64,3% and TLR4ex in 67% is below respective median. Past CMV strongly affected TLR2ex and moderately TLR4ex. On Day-0: in CMV+ we found no link of TLR2 ex and TLR4ex with EGFR; In CMV+ TLR2ex and TLR4ex were lower but Day-0 EGFR did not differ from H-TLR2 or H-TLR4ex. In CMVn: GFR-TLR4ex link was present with no similar in case of GFR-TLR2ex. In patients treated with tacrolimus CMV strongly affected TLR4ex, blurring CMV+/CMVn differences. Post F-up: in CMV+ with L-TLR4ex EGFR declined, there was no change of EGFR in H-TLR4ex; L/H-TLR2ex showed no differences in EGFR. In CMVn with H-TLR4ex EGFR rose, there was no change in L-TLR4ex. In case of TLR2ex we showed no similar differences. Regression analysis points out the impact of CMV+ and TLR4ex on eGFR and ΔEGFR. No similar impact of CMV+ and TLR2ex on eEGFR and ΔEGFR was found. Conclusion Conclusion: In the group who had a symptomatic CMV + infection, low TLR4 expression increases the risk of worsening EGFR. In CMVn, high TLR4 expression increases the chance of EGFR improvement. Historic CMV + strongly affects TLR2ex. However, TLR2ex cannot be used as a factor in assessing the risk of EGFR deterioration.

scholarly journals Peptidoglycan of Staphylococcus aureus Upregulates Monocyte Expression of CD14, Toll-Like Receptor 2 (TLR2), and TLR4 in Human Blood: Possible Implications for Priming of Lipopolysaccharide Signaling

2005 ◽  
Vol 73 (11) ◽  
pp. 7613-7619 ◽  
Author(s):  
J. S. Hadley ◽  
J. E. Wang ◽  
S. J. Foster ◽  
C. Thiemermann ◽  
C. J. Hinds
Keyword(s):  
Human Blood ◽  
Priming Effect ◽  
Ex Vivo ◽  
Experimental Period ◽  
Cytokine Release ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Tlr2 Expression ◽  
Twofold Increase ◽  
Toll Like Receptor 2

ABSTRACT Previous studies have indicated that peptidoglycan (PepG) from gram-positive bacteria can exert a priming effect on the innate immune response to lipopolysaccharide (LPS) from gram-negative bacteria. Here, we hypothesized that this priming effect may be preceded by enhanced expression of monocyte CD14, Toll-like receptor 2 (TLR2), and TLR4. In an ex vivo whole human blood model, we observed a substantial synergy between LPS and PepG in the release of tumor necrosis factor alpha and interleukin-1β (IL-1β) over the 24-h experimental period, whereas the effect on IL-8 and IL-10 release was more time dependent. The priming effect of PepG on cytokine release was preceded by a rapid upregulation of CD14, TLR2, and TLR4 expression on monocytes: at 3 hours there was a twofold increase in CD14 expression (P < 0.03), a fivefold increase in TLR2 expression (P < 0.03), and a twofold increase in TLR4 expression (P < 0.03). CD14 and TLR2 remained upregulated throughout the experimental period following exposure to PepG (P < 0.05). Only a transient upregulation of these monocyte receptors was observed following treatment with LPS or LPS plus PepG. In conclusion, the synergistic effect of LPS and PepG on cytokine release is preceded by a reciprocal upregulation of TLR2 and TLR4 by both bacterial cell wall components.

scholarly journals Decreased Toll-like Receptor (TLR) 2 and 4 Expression in Spermatozoa in Couples with Unexplained Recurrent Spontaneous Abortion (URSA)

2020 ◽  
Author(s):  
Nasrin Sereshki ◽  
Alireza Andalib ◽  
Ataollah Ghahiri ◽  
Ferdos Mehrabian ◽  
Roya Sherkat ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Recurrent Spontaneous Abortion ◽  
Control Group ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Tlr2 Expression ◽  
Unexplained Recurrent Spontaneous Abortion ◽  
Toll Like Receptor 2 ◽  
And Control ◽  
Reproductive Processes

Studies have shown that toll-like receptors (TLRs) play some important roles in reproductive processes such as ovulation, spermatogenesis, sperm capacitation, fertilization, and pregnancy to the best of our knowledge, no study has evaluated the expression and role of these molecules and their impairment in spermatozoa; accompanied by pregnancy complications such as recurrent spontaneous abortion (RSA). Therefore, this study investigates the alteration of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) expression in spermatozoa in men whose spouse have unexplained RSA. Fifteen fertile couples and fifteen couples with unexplained recurrent spontaneous abortion (URSA) were included in this study. The level of TLR2 and TLR4 expression in untreated and lipopolysaccharide (LPS) or PAM3CYS in treated spermatozoa were examined by flow cytometry. The results showed reduced expression of TLR4 in untreated spermatozoa and decreased LPS or PAM3CYS levels in treated spermatozoa in the URSA group compared to the control group. No significant differences were found in TLR2 expression of untreated spermatozoa in RSA and control groups. After the treatment of spermatozoa with LPS, the TLR2 expression was decreased in both groups. After the treatment of spermatozoa with PAM3CYS, the level of TLR2 expression was significantly increased in the URSA group; while no significant differences were shown in the control group in comparison to untreated spermatozoa. We have concluded that decreased TLR4 expression and a differently increased TLR2 expression in response to ligand treatment in spermatozoa is associated with URSA.

scholarly journals Relationship between toll-like receptor 2 Arg677Trp and Arg753Gln and toll-like receptor 4 Asp299Gly polymorphisms and cytomegalovirus infection

2014 ◽  
Vol 25 ◽  
pp. 11-15 ◽  
Author(s):  
Agnieszka Jabłońska ◽  
Edyta Paradowska ◽  
Mirosława Studzińska ◽  
Patrycja Suski ◽  
Dorota Nowakowska ◽  
...  
Keyword(s):  
Cytomegalovirus Infection ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Toll Like Receptor 2

scholarly journals FTO (Fat-Mass and Obesity-Associated Protein) Participates in Hemorrhage-Induced Thalamic Pain by Stabilizing Toll-Like Receptor 4 Expression in Thalamic Neurons

Stroke ◽  
2021 ◽  
Author(s):  
Ganglan Fu ◽  
Shibin Du ◽  
Tianfeng Huang ◽  
Minghui Cao ◽  
Xiaozhou Feng ◽  
...  
Keyword(s):  
Fat Mass ◽  
Rna Binding ◽  
Intraperitoneal Administration ◽  
Toll Like Receptor ◽  
Tlr4 Expression ◽  
Toll Like Receptor 4 ◽  
Thalamic Neurons ◽  
Adeno Associated Virus ◽  
Meclofenamic Acid ◽  
Thalamic Pain

Background and Purpose: Hemorrhage-caused gene changes in the thalamus likely contribute to thalamic pain genesis. RNA N 6 -methyladenosine modification is an additional layer of gene regulation. Whether FTO (fat-mass and obesity-associated protein), an N 6 -methyladenosine demethylase, participates in hemorrhage-induced thalamic pain is unknown. Methods: Expression of Fto mRNA and protein was assessed in mouse thalamus after hemorrhage caused by microinjection of Coll IV (type IV collagenase) into unilateral thalamus. Effect of intraperitoneal administration of meclofenamic acid (a FTO inhibitor) or microinjection of adeno-associated virus 5 (AAV5) expressing Cre into the thalamus of Fto fl/fl mice on the Coll IV microinjection–induced TLR4 (Toll-like receptor 4) upregulation and nociceptive hypersensitivity was examined. Effect of thalamic microinjection of AAV5 expressing Fto (AAV5- Fto ) on basal thalamic TLR4 expression and nociceptive thresholds was also analyzed. Additionally, level of N 6 -methyladenosine in Tlr4 mRNA and its binding to FTO or YTHDF2 (YTH N 6 -methyladenosine RNA binding protein 2) were observed. Results: FTO was detected in neuronal nuclei of thalamus. Level of FTO protein, but not mRNA, was time-dependently increased in the ipsilateral thalamus on days 1 to 14 after Coll IV microinjection. Intraperitoneal injection of meclofenamic acid or adeno-associated virus-5 expressing Cre microinjection into Fto fl/fl mouse thalamus attenuated the Coll IV microinjection–induced TLR4 upregulation and tissue damage in the ipsilateral thalamus and development and maintenance of nociceptive hypersensitivities on the contralateral side. Thalamic microinjection of AAV5- Fto increased TLR4 expression and elicited hypersensitivities to mechanical, heat and cold stimuli. Mechanistically, Coll IV microinjection produced an increase in FTO binding to Tlr4 mRNA, an FTO-dependent loss of N 6 -methyladenosine sites in Tlr4 mRNA and a reduction in the binding of YTHDF2 to Tlr4 mRNA in the ipsilateral thalamus. Conclusions: Our findings suggest that FTO participates in hemorrhage-induced thalamic pain by stabilizing TLR4 upregulation in thalamic neurons. FTO may be a potential target for the treatment of this disorder.

Sign in / Sign up

Export Citation Format

Share Document