Pathogen-Associated Molecular Pattern-Induced TLR2 and TLR4 Activation Increases Keratinocyte Production of Inflammatory Mediators and is Inhibited by Phosphatidylglycerol

Choudhary, Vivek; Griffith, Shantelle; Chen, Xunsheng; Bollag, Wendy B.

doi:10.1124/mol.119.118166

Cited by 21 publications

(30 citation statements)

References 34 publications

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“…Soybean saponin may be at least partially responsible for the inflammation by soybean meal 34 . Moreover, soy phosphatidylglycerol at a high concentration (50 μg/ml) enhanced the expression of TNF‐α mRNA and LPS‐induced expression of TNF‐α and IL‐1α mRNAs in mouse epidermal keratinocytes, 35 indicating that soy phosphatidylglycerol might cause skin inflammation. It is thus hypothesized that higher intake of pulses might be related to the development of PPP via the inflammatory effects of soybean ingredients.…”

Section: Discussionmentioning

confidence: 96%

Dietary habits in Japanese patients with palmoplantar pustulosis

Serizawa

Okazaki

Otsuka

et al. 2021

The Journal of Dermatology

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Palmoplantar pustulosis (PPP) is a chronic dermatitis characterized by sterile intra‐epidermal pustules associated with erythema and scales on the palms and soles. Tumor necrosis factor (TNF)‐α/interleukin (IL)‐23/IL‐17 inflammatory pathway may be involved in the pathogenesis of PPP, and the skin lesions manifest the enhanced expression of IL‐8 in keratinocytes and increased levels of antimicrobial peptide cathelicidin, leucine leucine‐37 in vesicles/pustules. Some PPP patients are associated with arthro‐osteitis, called pustulotic arthro‐osteitis (PAO). Dietary habits may modulate the pathogenesis of PPP, however, have not been investigated in PPP patients. We evaluated dietary habits in adult Japanese PPP patients, using a validated, brief‐type self‐administered diet history questionnaire, and compared their results to those of age‐ and sex‐matched healthy controls. The results in PPP patients with PAO were compared to those in the patients without. Japanese PPP patients showed higher body mass indices (BMIs), higher intakes of pulses and sugar/sweeteners, and lower intake of vitamin A, compared to those of healthy controls. The bivariate and multivariable logistic regression analysis showed that PPP was associated with high BMI, high intake of pulses, and low intake of vitamin A. The sodium intake and BMI were positively correlated with palmoplantar pustulosis area and severity index (PPPASI). The linear multivariate regression analysis revealed that sodium intake and BMI were predictors of PPPASI. The age and sodium intake in the patients with PAO were lower than those in the patients without. The bivariate and multivariable logistic regression analysis showed that PAO was negatively associated with age and sodium intake. This is the first study showing the dietary habits in patients with PPP. Further studies should clarify if the dietary intervention to correct the BMI and sodium intake will alter the progress of PPP.

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Section: Discussionmentioning

confidence: 96%

Dietary habits in Japanese patients with palmoplantar pustulosis

Serizawa

Okazaki

Otsuka

et al. 2021

The Journal of Dermatology

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“…1 ). Although it is not known whether PG has a similar inhibitory effect on the infectious capacity of SARS-CoV-2, a positive-sense single-strand RNA virus, the minimal effect of PG on the activation of TLR7/8 [32] , [34] would suggest that this phospholipid would likely not suppress innate immune system responses to the virus. Therefore, surfactant might be useful in preventing the spread of SARS-CoV-2 viral infection between infected and naïve cells within the lung without affecting the response to this infection, in addition to protecting against the damage caused by excessive inflammation and edema and the increased surface tension that eventually results from loss of surfactant.…”

Section: Additional Considerationsmentioning

confidence: 99%

“…Specifically, PG inhibits TLR2 and TLR4 activation by the DAMPs S100A9 and beta-defensin-2 [32] . PG can also inhibit TLR2 and TLR4 activation in response to PAMPs in several cell types and in TLR2 and TLR4 reporter cell lines [34] , with minimal effects on the activation of, or stimulation of inflammatory mediator expression by, other pattern recognition receptors, such as the TLR7/8 that recognizes single-stranded RNA. In addition, supplementation of surfactant with additional PG (to a molar percentage of 6%) preserves lung function and prevents alveolar epithelial injury and the expression of pro-fibrotic mediators in a neonatal pig triple injury model of ARDS [35] .…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, COVID-19 patients have been reported to exhibit elevated levels of tumor necrosis factor-alpha (TNFα) [2] , and drugs targeting pro-inflammatory mediators, such as interleukin (IL)-1 and IL-6 have been proposed or are in use for the treatment of COVID-19 [36] , [37] . PG has been shown to inhibit the expression of IL-1α, IL-1β, IL-6, and/or TNFα, as well as IL-8, interferon-gamma and/or macrophage inflammatory protein-2, in response to TLR activation by PAMPs and DAMPs [24] , [25] , [26] , [28] , [32] , [34] , [38] , [39] . In turn, several of these inflammatory mediators (e.g., IL-6 and TNFα) are also known to increase the levels of certain sPLA 2 s, in particular that encoded by the gene PLA2G2A [3] , which would decrease PG levels even further.…”

Section: Introductionmentioning

confidence: 99%

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Phosphatidylglycerol and surfactant: A potential treatment for COVID-19?

Bollag

Gonzales

2020

Medical Hypotheses

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A hypothesis concerning the potential utility of surfactant supplementation for the treatment of critically ill patients with COVID-19 is proposed, along with a brief summary of the data in the literature supporting this idea. It is thought that surfactant, which is already approved by the Food and Drug Administration for intratracheal administration to treat neonatal respiratory distress syndrome in pre-term infants, could benefit COVID-19-infected individuals by: (1) restoring surfactant damaged by lung infection and/or decreased due to the virus-induced death of the type II pneumocytes that produce it and (2) reducing surface tension to decrease the work of breathing and limit pulmonary edema. In addition, a constituent of surfactant, phosphatidylglycerol, could mitigate COVID-19-induced lung pathology by: (3) decreasing excessive innate immune system stimulation via its inhibition of toll-like receptor-2 and -4 activation by microbial components and cellular proteins released by damaged cells, thereby limiting inflammation and the resultant pulmonary edema, and (4) possibly blocking spread of the viral infection to non-infected cells in the lung. Therefore, it is suggested that surfactant preparations containing phosphatidylglycerol be tested for their ability to improve lung function in critically ill patients with COVID-19.

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“…inocytes. 27 The decrease of saturated fatty acids in sebum during pregnancy may be related to the synthesis of GP in cells (Figure 5A).…”

Section: F I G U R E 4 Amentioning

confidence: 99%

Study on the skin status of mid‐pregnancy women based on lipidomics

Chen

Huang

2020

J of Cosmetic Dermatology

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Background: Pregnancy is a complex physiological state and its unique changes in skin state have been discussed. Skin surface lipid (SSL) is an important molecular basis for this skin condition, and it affects skin condition in a number of ways, but there are no complete research data on it. Objectives: To analyze the lipidome profiles of SSL in pregnancies and controls in order to understand SSL changes in pregnancy. It will provide theoretical data of SSL on skin care and prevention of skin diseases during pregnancy. Methods: Ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and multivariate statistics were used to investigate the changes of SSL in pregnancy. Results: Results showed that there were significant differences (P < .05) in the lipidome between pregnancies and controls. Multivariate data analysis indicated that there were 20 important individual lipid species identified, and triglycerides (TGs) were the majority of differentiating lipid species. Conclusions: The increase of estrogen level in pregnancies antagonizes and inhibits the regulation of androgen on sebaceous gland, resulting in the decrease of sebum secretion and the weakening of skin barrier function. Besides, the decrease of saturated fatty acid content may be the main factor of the decrease of skin barrier function during pregnancy. Additionally, skin cells perform their self-regulation function to reduce or counteract abnormal state of the skin during pregnancy through the synthesis and secretion of more glycerophospholipids and ceramides.

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Pathogen-Associated Molecular Pattern-Induced TLR2 and TLR4 Activation Increases Keratinocyte Production of Inflammatory Mediators and is Inhibited by Phosphatidylglycerol

Cited by 21 publications

References 34 publications

Dietary habits in Japanese patients with palmoplantar pustulosis

Dietary habits in Japanese patients with palmoplantar pustulosis

Phosphatidylglycerol and surfactant: A potential treatment for COVID-19?

Study on the skin status of mid‐pregnancy women based on lipidomics

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