PMID- 26669856
OWN - NLM
STAT- MEDLINE
DCOM- 20160627
LR  - 20190828
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 12
DP  - 2015
TI  - Nontypeable Haemophilus influenzae-Induced MyD88 Short Expression Is Regulated by 
      Positive IKKbeta and CREB Pathways and Negative ERK1/2 Pathway.
PG  - e0144840
LID - 10.1371/journal.pone.0144840 [doi]
LID - e0144840
AB  - Airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) 
      are characterized by excessive inflammation and are exacerbated by nontypeable 
      Haemophilus influenzae (NTHi). Airway epithelial cells mount the initial innate 
      immune responses to invading pathogens and thus modulate inflammation. While 
      inflammation is necessary to eliminate a pathogen, excessive inflammation can 
      cause damage to the host tissue. Therefore, the inflammatory response must be 
      tightly regulated and deciphering the signaling pathways involved in this 
      response will enhance our understanding of the regulation of the host 
      inflammatory response. NTHi binds to TLR2 and signal propagation requires the 
      adaptor molecule myeloid differentiation factor 88 (MyD88). An alternative 
      spliced form of MyD88 is called MyD88 short (MyD88s) and has been identified in 
      macrophages and embryonic cell lines as a negative regulator of inflammation. 
      However, the role of MyD88s in NTHi-induced inflammation in airway epithelial 
      cells remains unknown. Here we show that NTHi induces MyD88s expression and 
      MyD88s is a negative regulator of inflammation in airway epithelial cells. We 
      further demonstrate that MyD88s is positively regulated by IKKbeta and CREB and 
      negatively regulated by ERK1/2 signaling pathways. Taken together these data 
      indicate that airway inflammation is controlled in a negative feedback manner 
      involving MyD88s and suggest that airway epithelial cells are essential to 
      maintain immune homeostasis.
FAU - Andrews, Carla S
AU  - Andrews CS
AD  - Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, 
      Georgia State University, Atlanta, Georgia, United States of America.
FAU - Miyata, Masanori
AU  - Miyata M
AD  - Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, 
      Georgia State University, Atlanta, Georgia, United States of America.
FAU - Susuki-Miyata, Seiko
AU  - Susuki-Miyata S
AD  - Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, 
      Georgia State University, Atlanta, Georgia, United States of America.
FAU - Lee, Byung-Cheol
AU  - Lee BC
AD  - Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, 
      Georgia State University, Atlanta, Georgia, United States of America.
FAU - Komatsu, Kensei
AU  - Komatsu K
AD  - Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, 
      Georgia State University, Atlanta, Georgia, United States of America.
FAU - Li, Jian-Dong
AU  - Li JD
AD  - Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, 
      Georgia State University, Atlanta, Georgia, United States of America.
LA  - eng
GR  - GM107529/GM/NIGMS NIH HHS/United States
GR  - R01 DC005843/DC/NIDCD NIH HHS/United States
GR  - R01 GM107529/GM/NIGMS NIH HHS/United States
GR  - DC004562/DC/NIDCD NIH HHS/United States
GR  - R01 DC013833/DC/NIDCD NIH HHS/United States
GR  - DC005843/DC/NIDCD NIH HHS/United States
GR  - R01 DC004562/DC/NIDCD NIH HHS/United States
GR  - DC013833/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20151215
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Animals
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - Epithelial Cells/metabolism/microbiology/pathology
MH  - Haemophilus Infections/complications/microbiology/pathology
MH  - Haemophilus influenzae/*physiology
MH  - Humans
MH  - I-kappa B Kinase/*metabolism
MH  - Inflammation/complications/pathology
MH  - Lung/pathology
MH  - *MAP Kinase Signaling System
MH  - Mice, Inbred C57BL
MH  - Models, Biological
MH  - Myeloid Differentiation Factor 88/*metabolism
PMC - PMC4684398
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/12/17 06:00
MHDA- 2016/06/28 06:00
PMCR- 2015/12/15
CRDT- 2015/12/17 06:00
PHST- 2015/08/05 00:00 [received]
PHST- 2015/11/24 00:00 [accepted]
PHST- 2015/12/17 06:00 [entrez]
PHST- 2015/12/17 06:00 [pubmed]
PHST- 2016/06/28 06:00 [medline]
PHST- 2015/12/15 00:00 [pmc-release]
AID - PONE-D-15-34428 [pii]
AID - 10.1371/journal.pone.0144840 [doi]
PST - epublish
SO  - PLoS One. 2015 Dec 15;10(12):e0144840. doi: 10.1371/journal.pone.0144840. 
      eCollection 2015.