Background. Hidradenitis suppurativa (HS) is a recurrent inflammatory disease of the apocrine sweat glands. Immune dysregulation probably contributes to the pathogenesis of HS. Aim. To harness mRNA expression arrays to investigate the transcriptome profile in HS compared with control skin. Methods. Illumina â HumanHT-12 v4 Expression BeadChips were used to measure mRNA expression in skin samples from HS (n = 10) and abdominoplasty (n = 11) skin specimens. Differentially expressed genes were detected by fitting genewise linear models to the normalized expression data and then modelling using the webbased software Ingenuity â Pathway Analysis. Results. The antimicrobial peptide Dermcidin and the cytokine regulator interleukin (IL)-37 were both significantly downregulated in the HS specimens (Dermcidin expression log ratio À3.93, expression P = 0.04; IL-37 expression log ratio À3.29, expression P < 0.001). Pathway analysis revealed the interferon-signalling pathway, leucocyte extravasation pathway, T helper 1 and 2 pathways and nuclear factor of activated T cells as the top-five upregulated pathways in the HS samples. Conclusion. Evaluation of transcriptome patterns in HS compared with normal skin demonstrated downregulation of the antimicrobial peptide Dermcidin and the innate immune regulator IL-37, as well as upregulation of interferon pathways and pathways of leucocyte activation.
Neutral lipids have been implicated in a host of potentially debilitating human diseases, such as heart disease, type-2 diabetes, and metabolic syndrome. Matrix-assisted laser desorption ionization (MALDI), the method-of-choice for mass spectrometry imaging (MSI), has led to remarkable success in imaging several lipid classes from biological tissue sections. However, due to ion suppression by phospholipids, MALDI has limited ability to efficiently ionize and image neutral lipids, such as triglycerides (TGs). To help overcome this obstacle, we have utilized silicon nanopost arrays (NAPA), a matrix-free laser desorption ionization (LDI) platform. Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory skin disease of the apocrine sweat glands. The ability of NAPA to efficiently ionize lipids is exploited in the analysis of human skin samples from sufferers of HS. Ionization by LDI from NAPA allows for the detection and imaging of a number of neutral lipid species, including TGs comprised of shorter, odd-chain fatty acids, which strongly suggests an increased bacterial load within the host tissue, as well as hexosylceramides (HexCers) and galabiosyl-/lactosylceramides that appear to be correlated with the presence of HS. Our results demonstrate that NAPA-LDI-MSI is capable of imaging and potentially differentiating healthy and diseased human skin tissues based on changes in detected neutral lipid composition.
Mass spectrometry imaging (MSI) is used increasingly to simultaneously detect a broad range of biomolecules while mapping their spatial distributions within biological tissue sections. Matrix-assisted laser desorption ionization (MALDI) is recognized as the method-of-choice for MSI applications due in part to its broad molecular coverage. In spite of the remarkable advantages offered by MALDI, imaging of neutral lipids, such as triglycerides (TGs), from tissue has remained a significant challenge due to ion suppression of TGs by phospholipids, e.g.
Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease of apocrine gland-bearing skin which affects approximately 1-4% of the population. Defective keratinocyte function has been postulated to play a role in HS pathogenesis. Using an in vitro scratch assay, differences between normal, HS, and chronic wound (CW) keratinocytes were evaluated. Normal keratinocytes exhibited faster scratch closure than HS or CW, with normal samples showing 93.8% closure at 96 hours compared to 80.8% in HS (p = 0.016) and 71.5% in CW (p = 0.0012). The keratinocyte viability was similar in normal and HS (91.12 ± 6.03% and 86.55 ± 3.28%, respectively, p = 0.1583), but reduced in CW (72.34 ± 13.12%, p = 0.0138). Furthermore, apoptosis measured by annexin V/propidium iodide, was higher in CW keratinocytes (32.10 ± 7.29% double negative cells compared to 68.67 ± 10.37% in normal and 55.10 ± 9.46% in HS, p = 0.0075). Normal keratinocytes exhibited a significantly higher level of IL-1α (352.83 ± 42.79 pg/ml) compared to HS (169.96 ± 61.62 pg/ml) and CW (128.23 ± 96.61 pg/ml, p = 0.004). HS keratinocytes exhibited significantly lower amounts of IL-22 (8.01 pg/ml) compared to normal (30.24 ± 10.09 pg/ml) and CW (22.20 ± 4.33 pg/ml, p = 0.0008), suggesting that defects in IL-22 signaling may play a role in HS pathogenesis. These findings support intrinsic differences in keratinocyte function in HS which cannot be attributed to reduced keratinocyte viability or increased apoptosis.
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