PMID- 22644107
OWN - NLM
STAT- MEDLINE
DCOM- 20130104
LR  - 20211021
IS  - 1432-1912 (Electronic)
IS  - 0028-1298 (Linking)
VI  - 385
IP  - 9
DP  - 2012 Sep
TI  - Intravenous immunoglobulin preparation attenuates LPS-induced production of 
      pro-inflammatory cytokines in human monocytic cells by modulating TLR4-mediated 
      signaling pathways.
PG  - 891-8
LID - 10.1007/s00210-012-0765-8 [doi]
AB  - Intravenous immunoglobulin (IVIG) has been used for the treatment of inflammatory 
      and autoimmune diseases. The ability to modulate cytokine production has been 
      formerly described as one of the mechanisms of its action. This study aimed to 
      investigate the effect of IVIG on the production of pro-inflammatory cytokines in 
      lipopolysaccharide (LPS)-stimulated monocytic cells. Peripheral blood mononuclear 
      cells (PBMCs) or THP-1 cells treated with phorbol myristate acetate (PMA) were 
      stimulated with LPS. The protein levels of pro-inflammatory cytokines [tumor 
      necrosis factor (TNF)-alpha, interleukin (IL)-6, and high-mobility group box 1 
      (HMGB1)] in the culture supernatants were determined using appropriate 
      enzyme-linked immunosorbent assay kits. The mRNA of TNF-alpha was determined by 
      reverse transcription-polymerase chain reaction. The phosphorylation of nuclear 
      factor kappa B (NF-kappaB) and the mitogen-activated protein kinases was examined by 
      Western blot analyses. IVIG suppressed the production of pro-inflammatory 
      cytokines such as TNF-alpha and IL-6 in LPS-stimulated PBMCs. Furthermore, IVIG 
      inhibited TNF-alpha, IL-6, and HMGB1 production from LPS-stimulated THP-1 cells 
      treated with PMA. In addition, Fc fragment prepared from the IVIG inhibited 
      production of these cytokines from the cells to the same degree as IVIG, whereas 
      Fab and F(ab')(2) fragments inhibited this only partially. We showed that IVIG 
      and Fc fragments suppressed LPS-induced signal transduction pathways involving 
      phosphorylation of NF-kappaB, p38, and c-Jun N-terminal kinase (JNK). Taken together, 
      our results suggest that IVIG attenuates LPS-induced cytokine production 
      predominantly mediated by its Fc region. The activity might be regulated by 
      inhibiting NF-kappaB, p38, and JNK pathways in human monocytic cells.
FAU - Murakami, Kazuki
AU  - Murakami K
AD  - Research and Developmental Division, Benesis Corporation, 3-16-89, Kashima, 
      Yodogawa-ku, Osaka-shi, Osaka, 532-8505, Japan. 
      Murakami.Kazuki@me.mt-pharma.co.jp
FAU - Suzuki, Chiaki
AU  - Suzuki C
FAU - Kobayashi, Fujio
AU  - Kobayashi F
FAU - Nakano, Atsushi
AU  - Nakano A
FAU - Fujii, Akihiro
AU  - Fujii A
FAU - Sakai, Kaoru
AU  - Sakai K
FAU - Imada, Teruaki
AU  - Imada T
LA  - eng
PT  - Journal Article
DEP - 20120531
PL  - Germany
TA  - Naunyn Schmiedebergs Arch Pharmacol
JT  - Naunyn-Schmiedeberg's archives of pharmacology
JID - 0326264
RN  - 0 (Cytokines)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Immunologic Factors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adult
MH  - Cell Line
MH  - Cells, Cultured
MH  - Cytokines/*biosynthesis
MH  - Humans
MH  - Immunoglobulin Fc Fragments/immunology
MH  - Immunoglobulins, Intravenous/immunology/*pharmacology
MH  - Immunologic Factors/*pharmacology
MH  - Leukocytes, Mononuclear/drug effects/metabolism
MH  - Lipopolysaccharides/toxicity
MH  - MAP Kinase Signaling System/drug effects
MH  - Monocytes/drug effects/metabolism
MH  - NF-kappa B/metabolism
MH  - Signal Transduction/drug effects
MH  - Toll-Like Receptor 4/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2012/05/31 06:00
MHDA- 2013/01/05 06:00
CRDT- 2012/05/31 06:00
PHST- 2012/03/08 00:00 [received]
PHST- 2012/05/18 00:00 [accepted]
PHST- 2012/05/31 06:00 [entrez]
PHST- 2012/05/31 06:00 [pubmed]
PHST- 2013/01/05 06:00 [medline]
AID - 10.1007/s00210-012-0765-8 [doi]
PST - ppublish
SO  - Naunyn Schmiedebergs Arch Pharmacol. 2012 Sep;385(9):891-8. doi: 
      10.1007/s00210-012-0765-8. Epub 2012 May 31.