PMID- 26525587
OWN - NLM
STAT- MEDLINE
DCOM- 20161012
LR  - 20220408
IS  - 1873-460X (Electronic)
IS  - 1056-8727 (Linking)
VI  - 30
IP  - 1
DP  - 2016 Jan-Feb
TI  - Increased expression of TLR9 associated with pro-inflammatory S100A8 and IL-8 in 
      diabetic wounds could lead to unresolved inflammation in type 2 diabetes mellitus 
      (T2DM) cases with impaired wound healing.
PG  - 99-108
LID - S1056-8727(15)00392-X [pii]
LID - 10.1016/j.jdiacomp.2015.10.002 [doi]
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by persistent 
      hyperglycemia which causes a chain of abrupt biochemical and physiological 
      changes. Immune dys-regulation is the hallmark of T2DM that could contribute to 
      prolonged inflammation causing transformation of wounds into non-healing chronic 
      ulcers. Toll like receptor -9 (TLR9) is a major receptor involved in innate 
      immune regulation. TLR9 activation induces release of pro-inflammatory molecules 
      like S100A8 and interleukin-8 (IL-8) by myeloid cells causing migration of 
      myeloid cells to the site of inflammation. We hypothesized that pro-inflammatory 
      S100A8 and IL-8 proteins could cause persistent inflammation in chronic wounds 
      like diabetic foot ulcer (DFU) and may contribute to impaired wound healing in 
      T2DM patients. MATERIALS AND METHODS: Expression of TLR9 and its downstream 
      effector molecules S100A8, and IL-8 were analyzed in chronic diabetic wound and 
      non-diabetic control wound tissue samples by semiquantitative reverse 
      transcriptase - polymerase chain reaction (RT-PCR), quantitative RT-PCR, western 
      blot and immunofluorescence. CD11b(+)CD33(+) myeloid cells were analyzed by flow 
      cytometry. RESULTS: TLR9 message and protein were higher in diabetic wounds 
      compared to control wounds (p=0.03, t=2.21 for TLR9 mRNA; p=<0.001, t=4.21 for 
      TLR9 protein). TLR9 down-stream effector molecules S100A8 and IL-8 were also 
      increased in diabetic wounds (p=0.003, t=3.1 for S100A8 mRNA; p=0.04, t=2.04 for 
      IL-8). CD11b(+) CD33(+) myeloid cells were decreased in T2DM as compared to 
      non-diabetic controls (p=0.001, t=3.6). DFU subjects had higher levels of 
      CD11b(+) CD33(+) myeloid cells as compared to non-DFU T2DM control (p=0.003, 
      t=2.8). Infection in the wound microenvironment could be the cause of increase in 
      CD11b(+)CD33(+) myeloid cells in DFU (p=0.03, t=2.5). CONCLUSION: The 
      up-regulation of myeloid cell-derived pro-inflammatory molecules S100A8 and IL-8 
      in combination with lower levels of CD11b(+) CD33(+) myeloid cells may cause the 
      impairment of wound healing in T2DM subjects leading to chronic ulcers.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Singh, Kanhaiya
AU  - Singh K
AD  - Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, 
      221005, India.
FAU - Agrawal, Neeraj K
AU  - Agrawal NK
AD  - Department of Endocrinology and Metabolism, Institute of Medical Sciences, 
      Banaras Hindu University, Varanasi, 221005, India.
FAU - Gupta, Sanjeev K
AU  - Gupta SK
AD  - Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, 
      Varanasi, 221005, India.
FAU - Sinha, Pratima
AU  - Sinha P
AD  - Department of Biological Sciences, University of Maryland Baltimore County 
      Baltimore, MD, USA. Electronic address: sinhapratima2008@gmail.com.
FAU - Singh, Kiran
AU  - Singh K
AD  - Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi, 
      221005, India. Electronic address: singhk4@rediffmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151009
PL  - United States
TA  - J Diabetes Complications
JT  - Journal of diabetes and its complications
JID - 9204583
RN  - 0 (CD11b Antigen)
RN  - 0 (CD33 protein, human)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Calgranulin A)
RN  - 0 (ITGAM protein, human)
RN  - 0 (Interleukin-8)
RN  - 0 (Sialic Acid Binding Ig-like Lectin 3)
RN  - 0 (TLR9 protein, human)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biopsy
MH  - CD11b Antigen/metabolism
MH  - Calgranulin A/*metabolism
MH  - Diabetes Mellitus, Type 2/complications/immunology/*metabolism/pathology
MH  - Diabetic Foot/immunology/metabolism/microbiology/pathology
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Immunity, Innate
MH  - Interleukin-8/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Myeloid Cells/immunology/metabolism/pathology
MH  - Sialic Acid Binding Ig-like Lectin 3/metabolism
MH  - Toll-Like Receptor 9/genetics/*metabolism
MH  - *Up-Regulation
MH  - *Wound Healing
MH  - Wound Infection/immunology/metabolism/microbiology/pathology
OTO - NOTNLM
OT  - CD11b(+) CD33(+) myeloid cells
OT  - IL-8
OT  - S100A8
OT  - TLR9
OT  - Type 2 diabetes mellitus
OT  - Wound healing impairment
EDAT- 2015/11/04 06:00
MHDA- 2016/10/13 06:00
CRDT- 2015/11/04 06:00
PHST- 2015/08/05 00:00 [received]
PHST- 2015/09/24 00:00 [revised]
PHST- 2015/10/04 00:00 [accepted]
PHST- 2015/11/04 06:00 [entrez]
PHST- 2015/11/04 06:00 [pubmed]
PHST- 2016/10/13 06:00 [medline]
AID - S1056-8727(15)00392-X [pii]
AID - 10.1016/j.jdiacomp.2015.10.002 [doi]
PST - ppublish
SO  - J Diabetes Complications. 2016 Jan-Feb;30(1):99-108. doi: 
      10.1016/j.jdiacomp.2015.10.002. Epub 2015 Oct 9.