Inherent differences in keratinocyte function in hidradenitis suppurativa: Evidence for the role of IL-22 in disease pathogenesis

ABSTRACT

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.

KEYWORDS:

• Wound
• hidradenitis suppurativa
• keratinocyte
• IL-22
• IL-1α
• VEGF

Abbreviations

HS	=	(Hidradenitis Suppurativa),
CW	=	(chronic wounds),
N	=	(normal),
IL	=	(interleukin),
MFI	=	(mean fluorescence index),
FITC	=	(fluorescein isothiocyanate),
PI	=	(propidium iodide),
IFN-γ	=	(Interferon-gamma),
VEGF	=	(vascular endothelial growth factor).

Acknowledgments

Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.

IRB Status

Approved by the George Washington University Institutional Review Board (041408 and 101419).

Declaration of interest

The authors declare no conflict of interest.

Funding

This work was in part supported by award R01NR013888 from the National Institute of Nursing Research and by award number UL1 TR000075 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through the Clinical and Translational Science Awards Program (CTSA).

Additional information

Funding

This work was in part supported by award R01NR013888 from the National Institute of Nursing Research and by award number UL1 TR000075 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through the Clinical and Translational Science Awards Program (CTSA).