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The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) controls the expression of genes involved in the regulation of lipid and glucose metabolism, cell ...proliferation/differentiation as well as inflammatory pathways. Pivotal studies in human sebocytes and isolated sebaceous glands have raised the interesting possibility that compounds acting on PPARγ can modulate sebaceous lipids and inflammation and, as such, may be useful in the treatment of acne. To investigate the role of this receptor in the regulation of lipid synthesis, proliferation and inflammation, we used the SZ95 sebaceous gland cell line stimulated with insulin. In sebocytes, insulin signaling activated the phosphatidylinositide 3-kinase-Akt (PI3K/Akt) and mammalian target of rapamycin (mTOR) pathways, which, in turn, induced high protein/lipid synthesis, increased cell growth and proliferation as well as inflammation. As regards lipogenesis, insulin initially stimulated the formation of unsaturated lipids and then the neosynthesis of lipids. The results showed, that the modulation of PPARγ, counteracted the insulin-induced altered lipogenesis, evident through a decrease in gene expression of key enzymes responsible for the synthesis of fatty acids, and through a reduction of lipid species synthesis analyzed by Oil/Nile Red staining and GC–MS. PPARγ modulation also regulated the insulin-induced proliferation, inhibiting the cell cycle progression and p21WAF1/CIP1 (p21) protein reduction. Moreover, the expression of inflammatory cytokines, induced by insulin or lipopolysaccharide (LPS), was down-modulated. In PPARγ-deficient cells or in the presence of GW9662 antagonist, all these observed effects were abolished, indicating that PPARγ activation plays a role in regulating alteration of lipogenesis, cell proliferation and inflammatory signaling. We demonstrated that selective modulation of PPARγ activity is likely to represent a therapeutic strategy for the treatment of acne.
Summary
Background
Leptin, the adipocyte‐secreted hormone that regulates weight, is known to link lipid metabolism with inflammation in various cell types. However, its role in human sebocytes has ...not yet been investigated.
Objectives
The purpose of this study was to investigate the effects of leptin in human sebaceous gland biology.
Methods
Expression of the long form of the leptin receptor (Ob‐Rb) was detected by real‐time quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR) and immunochemistry. Lipid analysis was by high‐performance thin‐layer chromatography, gas chromatography–mass spectrometry and time‐of‐flight mass spectrometer mass detection. Lipid bodies were visualized by BODIPY staining using fluorescent microscopy and measured by flow cytometry. Interleukin (IL)‐6 and IL‐8 mRNA levels were assessed by real‐time qRT‐PCR and their release was evaluated by enzyme‐linked immunosorbent assay. Cyclooxygenase (COX)‐2 and 5‐lipooxygenase (LOX) protein expression and phosphorylation of p65 and signal transducer and activator of transcription (STAT)‐3 were determined by Western blot analysis.
Results
Expression of Ob‐Rb was detected in human sebaceous glands and in cultured human SZ95 sebocytes. The treatment of SZ95 sebocytes with leptin led to enlarged intracellular lipid bodies, increased ratios of unsaturated/saturated fatty acids and decreased vitamin E levels. Further supporting a proinflammatory role, leptin induced COX‐2 and 5‐LOX expression in SZ95 sebocytes and augmented the production of IL‐6 and IL‐8 cytokines. On leptin treatment, the STAT‐3 and nuclear factor‐κB pathways were activated, indicating that these known leptin signalling pathways are active in human sebocytes.
Conclusions
Our findings suggest that leptin signalling may be involved in the proinflammatory regulation of sebaceous lipid metabolism and the induction of inflammatory enzymes and cytokines.
What's already known about this topic?
Leptin is an adipocyte‐secreted hormone that regulates weight.
Leptin is known to link lipid metabolism with inflammation in various cell types.
Sebaceous glands are capable of responding to different stimuli by an altered secretion of lipids and production of inflammatory mediators.
What does this study add?
Leptin was recognized as a possible proinflammatory player in sebaceous gland biology.
Sebocytes responded to leptin stimulation with proinflammatory changes in the sebaceous lipid profile and with an increased expression of inflammatory enzymes and cytokines.
Two strains of Arcobacter butzleri, ATCC 49616 and an environmental isolate, became nonculturable in seawater microcosms at 4°C by 20 days and at room temperature by 14 days. Nonculturable cells were ...viable for up to 270 days of incubation in microcosms. Resuscitation of A. butzleri cells from microcosms at both temperatures was achieved 9 days after nutrient addition.
Background
Sebum plays a key role in the initiation of the acne lesions. Oxidized sebum lipids cause keratynocytes hyperproliferation and inflammatory cytokines release. Association between sebum ...oxidation and comedogenesis has been little investigated in comedonal acne.
Objectives
Evaluation of sebum oxidation parameters and levels of inflammatory cytokines (IL‐1α) in patients with mild comedonal acne (MCA) before and after the treatment with a mixed RetinSphere®‐ vitamin E formulation.
Methods
Sebum excretion rate (SER), squalene concentration, and oxidation degree of sebum were measured in 18 MCA patients and 10 controls. IL‐1α levels in the stratum corneum were measured in both lesional and non‐lesional facial areas of MCA patients. Sebum parameters and IL‐1α were measured at week 4 of topical treatment. Reflectance confocal microscopy (RCM) was performed in a subset of four patients at the baseline and at week 4 and all patients were assessed clinically before and following the 8 week‐treatment.
Results
Sebum excretion rate and squalene concentration were comparable between MCA patients and healthy controls. Lipid peroxidation (LPO) and the percentage of oxidized squalene (SQOX) were significantly elevated in the sebum of MCA patients. The concentration of the proinflammatory cytokine IL‐1α in stratum corneum was significantly higher in the lesional area compared with non‐lesional area of the MCA patients at the baseline. At week 4, while SER and squalene concentration did not vary significantly, the LPO levels and the SQOX percentage resulted decreased at a significant extent. Following the treatment, IL‐1α concentration in the lesional area reached values comparable to those of unaffected areas. Consistent with the biochemical data, RCM showed the reduction of hyperkeratinization and of inflammatory cells infiltration of the adnexal structures epithelium, significant clinical improvement was recorded at week 8.
Conclusion
The data further support the involvement of lipid oxidation and particularly by‐products of squalene oxidation in comedogenesis.
Aims: To evaluate the presence of Arcobacter spp. in different biological samples from domestic cats in Southern Italy by using a species‐specific PCR assay and thus to elucidate their potential ...significance as sources of human infection.
Methods and Results: We investigated the prevalence of Arcobacter DNA in oral swabs, in peripheral blood samples and fine needle lymph node aspirate specimens from 85 cats of which 17 were clinically healthy and 68 had clinical signs of oral disease or lymphadenomegaly. Overall, molecular analysis has shown that Arcobacter‐specific DNA was found in 78·8% (67 of 85) of all the cats. In the 67 Arcobacter‐positive cats, 66 (77·6%) and 29 (34·1%) were found positive for Arcobacter butzleri and Arcobacter cryaerophilus, respectively. None of the examined samples gave a PCR product for Arcobacter skirrowii.
Conclusions: This study demonstrates that pet cats commonly carry Arcobacter in the oral cavity. According to the clinical data, the Arcobacter detection results showed no significant difference between cats with oral pathology and those suffering from other different pathologies.
Significance and Impact of the Study: Pet cats harbour Arcobacter spp. and may play a role in their dissemination in the domestic habitat. The high prevalence in a limited number of cat samples in this study may be of significance.
To evaluate the reliability of culture-independent methods in comparison with culture-dependent ones for the detection of Arcobacter spp. in estuarine waters of Southern Italy. PCR and fluorescent in ...situ hybridization (FISH) procedures were used to detect arcobacters directly in water samples and after enrichment cultures. The samples totally were positive by molecular methods (PCR and FISH) but only 75% were culture positive, confirming the limitation of these latter to detect Arcobacter spp. in natural samples. Culturable arcobacters were retrieved in all times except in July, and isolated species were ascribed only to Arcobacter cryaerophilus. Culturable and nonculturable forms of Arcobacter in the estuarine environment were present. PCR assays were more sensitive than traditional culture in detecting Arcobacter butzleri and A. cryaerophilus. FISH comparatively to PCR technique may provide information about cell morphology and viability of single cells. Our investigation indicates the existence of an environmental reservoir of potential pathogenic arcobacters in an estuarine Italian area, which may survive under a viable but not culturable state.
The role of lipids in maize – Fusarium verticillioides interaction and fumonisin production in natural field conditions were investigated. In 2010, ten maize hybrids were grown in fields located in 3 ...districts in Northern Italy and sampled at 4 growing stages, from early dough to full ripe. Chemical composition, fungal incidence and free and hidden fumonisin contamination were determined in all grain samples. All the hybrids considered within this study showed a strong fungal incidence, with Fusarium section Liseola as prevalent, already at the early dough maturity and along the ripening period. Fumonisins accumulated over the growing season and reached the maximum level at the full ripe stage; hidden fumonisins were found significant in all the considered samples (~57% of the free form at harvest). Hybrid H9 showed more than 50% of kernels infected by Aspergillus flavus and no hidden fumonisins were detected. This finding stresses the relevance of monitoring both free and total fumonisins for a comprehensive assessment of consumer exposure to mycotoxins. Previous studies showed a positive correlation between the content of linoleic acid and fumonisin accumulation into maize kernels infected with Fusarium section Liseola. Hence, an untargeted and targeted lipid analysis of maize kernels along the growing season and at harvest was performed. Results suggested a significant involvement of lipid composition of maize kernels in fungal infection and toxin accumulation. Specifically, mass spectrometry data pinpointed that at least 4 lipid entities might differentiate high-contaminated from low-contaminated samples when the cut-off of 2,000 μg/kg of fumonisins was selected. Among them, the oxylipin 9-HODE and three sphingolipids were identified. These results suggest that sphingolipid and oxylipin metabolism in maize kernels interferes with F. verticillioides growth and fumonisin production in plants growing in field.
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