PMID- 34424458
OWN - NLM
STAT- MEDLINE
DCOM- 20220719
LR  - 20220819
IS  - 1573-2568 (Electronic)
IS  - 0163-2116 (Linking)
VI  - 67
IP  - 8
DP  - 2022 Aug
TI  - Repeated Stimulation of Toll-Like Receptor 2 and Dectin-1 Induces Chronic 
      Pancreatitis in Mice Through the Participation of Acquired Immunity.
PG  - 3783-3796
LID - 10.1007/s10620-021-07186-w [doi]
AB  - BACKGROUND: Stimulation of Toll-like receptor 3 (TLR3) induces 
      autoimmune-mediated pancreatitis in susceptible mice, whereas stimulation of TLR4 
      causes nonautoimmune-mediated pancreatitis. However, the effects of TLR2 
      stimulation on the pancreas are unknown. AIMS: We investigated the role of TLR2 
      stimulation on pancreatic damage by repeatedly stimulating mice with TLR2 
      ligands. METHODS: Wild-type (WT) and interleukin 10-deficient (IL-10-knockout 
      (KO)) mice were administered zymosan and lipoteichoic acid (LTA) 
      intraperitoneally at various doses twice weekly for 4 weeks. Syngeneic 
      T-cell-deficient mice, B-cell-deficient mice, recombination activating gene 
      2-deficient (RAG2-KO) mice and RAG2-KO mice that had been reconstituted with 
      CD4(+) or CD8(+) T cells isolated from WT mice were treated with zymosan 
      similarly. Mice were killed, the severity of pancreatitis was graded 
      histologically, and serum cytokine levels were measured. RESULTS: Repeated 
      administration of zymosan induced pancreatitis dose dependently in both WT and 
      IL-10-KO mice. Administration of LTA induced pancreatitis only in IL-10-KO mice. 
      Adoptive transfer of splenocytes obtained from IL-10-KO mice with pancreatitis 
      did not cause pancreatitis in recipient RAG2-KO mice. Pancreatitis was scarcely 
      observed in RAG2-KO mice and was attenuated in T-cell-deficient and 
      B-cell-deficient mice compared with WT mice. A single administration of zymosan 
      significantly increased the serum level of monocyte chemoattractant protein 1 
      (MCP-1) in WT mice. CONCLUSIONS: Repeated stimulation of TLR2 and dectin-1 
      induced nonautoimmune-mediated pancreatitis in mice. Participation of acquired 
      immunity seems to play an important role in the pathogenesis of pancreatitis in 
      association with the increase in serum MCP-1 level.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Takeo, Masahiro
AU  - Takeo M
AD  - Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 
      Shinmachi, Hirakata, Osaka, Japan.
FAU - Nishio, Akiyoshi
AU  - Nishio A
AUID- ORCID: 0000-0002-2834-4863
AD  - Department of Gastroenterology and Hepatology, Kansai Medical University Medical 
      Center, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan. 
      nishioa@takii.kmu.ac.jp.
FAU - Masuda, Masataka
AU  - Masuda M
AD  - Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 
      Shinmachi, Hirakata, Osaka, Japan.
FAU - Aoi, Kazunori
AU  - Aoi K
AD  - Department of Gastroenterology and Hepatology, Kansai Medical University Medical 
      Center, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan.
FAU - Okazaki, Takashi
AU  - Okazaki T
AD  - Department of Gastroenterology and Hepatology, Kansai Medical University Medical 
      Center, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan.
FAU - Fukui, Toshiro
AU  - Fukui T
AD  - Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 
      Shinmachi, Hirakata, Osaka, Japan.
FAU - Uchida, Kazushige
AU  - Uchida K
AD  - Department of Gastroenterology and Hepatology, Kochi Medical School, 185-1 Kohasu 
      Okocho, Nankoku, Kochi, Japan.
FAU - Naganuma, Makoto
AU  - Naganuma M
AD  - Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 
      Shinmachi, Hirakata, Osaka, Japan.
FAU - Okazaki, Kazuichi
AU  - Okazaki K
AD  - Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 
      Shinmachi, Hirakata, Osaka, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210823
PL  - United States
TA  - Dig Dis Sci
JT  - Digestive diseases and sciences
JID - 7902782
RN  - 0 (Clec7a protein, mouse)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 130068-27-8 (Interleukin-10)
RN  - 9010-72-4 (Zymosan)
SB  - IM
MH  - *Adaptive Immunity
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - Interleukin-10/genetics
MH  - *Lectins, C-Type
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - *Pancreatitis, Chronic/pathology
MH  - *Toll-Like Receptor 2/genetics/metabolism
MH  - Zymosan
OTO - NOTNLM
OT  - Acquired immunity
OT  - Chronic pancreatitis
OT  - Dectin-1
OT  - Monocyte chemoattractant protein-1
OT  - Toll-like receptor
OT  - Zymosan
EDAT- 2021/08/24 06:00
MHDA- 2022/07/20 06:00
CRDT- 2021/08/23 12:31
PHST- 2020/12/10 00:00 [received]
PHST- 2021/07/20 00:00 [accepted]
PHST- 2021/08/24 06:00 [pubmed]
PHST- 2022/07/20 06:00 [medline]
PHST- 2021/08/23 12:31 [entrez]
AID - 10.1007/s10620-021-07186-w [pii]
AID - 10.1007/s10620-021-07186-w [doi]
PST - ppublish
SO  - Dig Dis Sci. 2022 Aug;67(8):3783-3796. doi: 10.1007/s10620-021-07186-w. Epub 2021 
      Aug 23.