Expatiating the molecular approaches of HMGB1 in diabetes mellitus: Highlighting signalling pathways via RAGE and TLRs

Behl, Tapan; Sharma, Eshita; Sehgal, Aayush; Kaur, Ishnoor; Kumar, Arun; Arora, Raksha; Pal, Giridhari; Kakkar, Mohit Kumar; Kumar, Ravinder; Bungău, Simona

doi:10.1007/s11033-020-06130-x

Cited by 25 publications

(13 citation statements)

References 106 publications

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“…In addition to the interaction with RAGE, several members of the TLR family, including TLR2, 4, 5, and 9, are also able to interact with HMGB1 [ 63 – 66 ]. HMGB1 therefore acts by activating RAGE and TLRs, contributing to the production of pro-inflammatory mediators associated with DM [ 67 ].…”

Section: Main Findings and Discussionmentioning

confidence: 99%

Interplay Among the Oral Microbiome, Oral Cavity Conditions, the Host Immune Response, Diabetes Mellitus, and Its Associated-Risk Factors—An Overview

Negrini

Carlos

Duque

et al. 2021

Front. Oral. Health

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This comprehensive review of the literature aimed to investigate the interplay between the oral microbiome, oral cavity conditions, and host immune response in Diabetes mellitus (DM). Moreover, this review also aimed to investigate how DM related risk factors, such as advanced age, hyperglycemia, hyperlipidemia, obesity, hypertension and polycystic ovary syndrome (PCOS), act in promoting or modifying specific mechanisms that could potentially perpetuate both altered systemic and oral conditions. We found that poorly controlled glycemic index may exert a negative effect on the immune system of affected individuals, leading to a deficient immune response or to an exacerbation of the inflammatory response exacerbating DM-related complications. Hyperglycemia induces alterations in the oral microbiome since poor glycemic control is associated with increased levels and frequencies of periodontal pathogens in the subgingival biofilm of individuals with DM. A bidirectional relationship between periodontal diseases and DM has been suggested: DM patients may have an exaggerated inflammatory response, poor repair and bone resorption that aggravates periodontal disease whereas the increased levels of systemic pro-inflammatory mediators found in individuals affected with periodontal disease exacerbates insulin resistance. SARS-CoV-2 infection may represent an aggravating factor for individuals with DM. Individuals with DM tend to have low salivary flow and a high prevalence of xerostomia, but the association between prevalence/experience of dental caries and DM is still unclear. DM has also been associated to the development of lesions in the oral mucosa, especially potentially malignant ones and those associated with fungal infections. Obesity plays an important role in the induction and progression of DM. Co-affected obese and DM individuals tend to present worse oral health conditions. A decrease in HDL and, an increase in triglycerides bloodstream levels seem to be associated with an increase on the load of periodontopathogens on oral cavity. Moreover, DM may increase the likelihood of halitosis. Prevalence of impaired taste perception and impaired smell recognition tend to be greater in DM patients. An important interplay among oral cavity microbiome, DM, obesity and hypertension has been proposed as the reduction of nitrate into nitrite, in addition to contribute to lowering of blood pressure, reduces oxidative stress and increases insulin secretion, being these effects desirable for the control of obesity and DM. Women with PCOS tend to present a distinct oral microbial composition and an elevated systemic response to selective members of this microbial community, but the association between oral microbiome, PCOS are DM is still unknown. The results of the studies presented in this review suggest the interplay among the oral microbiome, oral cavity conditions, host immune response and DM and some of the DM associated risk factors exist. DM individuals need to be encouraged and motivated for an adequate oral health care. In addition, these results show the importance of adopting multidisciplinary management of DM and of strengthening physicians-dentists relationship focusing on both systemic and on oral cavity conditions of DM patients.

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Section: Main Findings and Discussionmentioning

confidence: 99%

Interplay Among the Oral Microbiome, Oral Cavity Conditions, the Host Immune Response, Diabetes Mellitus, and Its Associated-Risk Factors—An Overview

Negrini

Carlos

Duque

et al. 2021

Front. Oral. Health

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“…TLR2 and TLR4 as receptors for HMGB1 participate in immune responses in macrophages [ 25 ]. MG infection significantly upregulated TLR2 but suppressed TLR4 expression ( Figure 3 A).…”

Section: Resultsmentioning

confidence: 99%

Extracellular HMGB1 as Inflammatory Mediator in the Progression of Mycoplasma Gallisepticum Infection

Wang

et al. 2022

Cells

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High-mobility group box 1 (HMGB1), a member of damage-associated molecular patterns (DAMPs), is involved in the immune regulation of several infectious diseases. Mycoplasma gallisepticum (MG) infection is proved to cause an abnormal immune response, but the role of HMGB1 in MG-induced chronic respiratory disease (CRD) is unclear. In this study, we found that HMGB1 was released from the nucleus to the extracellular in macrophages upon infection with MG. Extracellular HMGB1 bound to TLR2 activating the NF-κB pathway triggering a severe inflammatory storm and promoting the progression of MG infection. More importantly, TLR4 could be activated by HMGB1 to trigger immune disorders after TLR2 was silenced. This disease process could be interrupted by ethyl pyruvate (EP) inhibition of HMGB1 release or glycyrrhizic acid (GA). Furthermore, treatment of MG-infected chickens with GA significantly alleviated immune organ damage. In conclusion, we demonstrate that HMGB1 is secreted extracellularly to form an inflammatory environment upon MG infection, triggering a further cellular inflammatory storm in a positive feedback approach. Blocking MG-induced HMGB1 release or suppression downstream of the HMGB1-TLR2/TLR4 axis may be a promising novel strategy for the treatment of CRD. Furthermore, this study may provide a theoretical reference for understanding non-LPS-activated TLR4 events.

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“…The recruitment and phosphorylation of IRAK1 are specific to the MyD88-dependent signaling pathway ( Li and Verma, 2002 ). Bhel et al ( Behl et al, 2021 ) described how LMWH reduced HMGB1 expression during inflammation by negatively mediating NETosis. LMWH could decrease inflammatory factors in diabetes by inhibiting the HMGB1-TLR4-NF-κB pathway, which gave rise to our study of the mechanism of interaction of LMWH and TLR4 in acute sinusitis.…”

Section: Discussionmentioning

confidence: 99%

Low Molecular Weight Heparin Improves the Inflammatory State of Acute Sinusitis Rats Through Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway

Jiao

et al. 2021

Front. Pharmacol.

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Introduction: Low molecular weight heparin (LMWH), a natural sulfated glycosaminoglycan with an affinity for proangiogenic factors, is produced by chemical or enzymatic depolymerization of unfractionated heparin (UFH). Known for its anticoagulant effects, LMWH has recently been reported to have a strong anti-inflammatory effect on colitis, myocarditis, and airway inflammation. However, as a newly-developed drug, its anti-inflammatory mechanism in upper respiratory tract inflammation has not been well-studied.Methods: SD rats were randomly divided into control and experimental groups. The experimental group was established by building an acute nasal sinusitis model with expansion sponges mixed with Streptococcus pneumoniae. Then the experimental group rats were subcutaneously injected with different concentrations of LMWH. After seven consecutive days of injection, some rats were sacrificed, and blood and nasal mucosa samples were taken to determine their inflammation status. The remaining acute sinusitis rats were randomly selected for a week of nasal irrigation with normal saline or saline mixed with different concentrations of LMWH. One week later, rats were sacrificed, and samples of blood and nasal mucosa were taken to determine the inflammation status.Results: Rat nasal mucosa in the model group had obvious inflammation. The degree of nasal mucosa inflammation damage in the experimental group was lower than in the experimental control group, proving that LMWH has a protective effect on the nasal mucosa and that the effect correlates with dosage. Irrigation of the nose with saline mixed with LMWH can improve the anti-inflammatory effect. Protein related to the TLR4-MyD88-NF-κB signaling pathway was activated in the acute sinusitis rat model, and LMWH can significantly inhibit its expression.Conclusion: This is the first report of the anti-inflammatory effect of LMWH in acute upper respiratory tract inflammation, together with an explanation of its anti-inflammatory mechanism. The findings contribute a theoretical basis for its potential anti-tumor effect.

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Expatiating the molecular approaches of HMGB1 in diabetes mellitus: Highlighting signalling pathways via RAGE and TLRs

Cited by 25 publications

References 106 publications

Interplay Among the Oral Microbiome, Oral Cavity Conditions, the Host Immune Response, Diabetes Mellitus, and Its Associated-Risk Factors—An Overview

Interplay Among the Oral Microbiome, Oral Cavity Conditions, the Host Immune Response, Diabetes Mellitus, and Its Associated-Risk Factors—An Overview

Extracellular HMGB1 as Inflammatory Mediator in the Progression of Mycoplasma Gallisepticum Infection

Low Molecular Weight Heparin Improves the Inflammatory State of Acute Sinusitis Rats Through Inhibiting the TLR4-MyD88-NF-κB Signaling Pathway

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