PMID- 18542100
OWN - NLM
STAT- MEDLINE
DCOM- 20081020
LR  - 20220410
IS  - 0818-9641 (Print)
IS  - 0818-9641 (Linking)
VI  - 86
IP  - 6
DP  - 2008 Aug-Sep
TI  - Role of phosphatidylinositol-3-kinase-gamma (PI3Kgamma)-mediated pathway in 
      17beta-estradiol-induced killing of L. mexicana in macrophages from C57BL/6 mice.
PG  - 539-43
LID - 10.1038/icb.2008.39 [doi]
AB  - We recently demonstrated that 17beta-estradiol (E2) enhances killing of 
      Leishmania mexicana in macrophages from both male and female DBA/2 mouse by 
      increasing nitric oxide (NO) production. Here, we analyzed the effect of E2 on 
      leishmanicidal activity and cytokine production by bone marrow-derived 
      macrophages (BMDMs) from male and female C57BL/6 mice in vitro, specifically 
      examining the role of phosphatidylinositol-3-kinase-gamma (PI3Kgamma) in 
      E2-induced parasite killing. Unlike its effect on macrophages from both male and 
      female DBA/2 mice, E2 only increased leishmanicidal activity in macrophages from 
      female C57BL/6 mice, which was evident by a significant reduction in both 
      infection rates and infection levels compared to sham controls. E2-treated BMDMs 
      from female C57BL/6 mice expressed higher levels of interferon-gammaRalpha, and 
      also produced more interleukin (IL)-12, IL-6 and NO than both the sham controls 
      and E2-treated male-derived macrophages. Sham-treated BMDMs from female 
      PI3Kgamma-/- C57BL/6 mice displayed lower infection rates and infection levels 
      compared to sham-treated wild-type (WT) macrophages. However E2, unlike its 
      effect on macrophages from female WT C57BL/6 mice, failed to reduce infection 
      rates and infection levels in BMDMs from female PI3Kgamma-/- mice. Interestingly, 
      E2-treated BMDMs from female C57BL/6 mice produced significant amounts of 
      inflammatory cytokines and NO in levels comparable to those observed in 
      sham-treated PI3Kgamma-deficient macrophages as well as E2-treated macrophages 
      from WT mice. These findings show that E2 exerts a distinct effect on 
      leishmanicidal activity of macrophages from male versus female C57BL/6 mice. In 
      addition, they suggest that PI3Kgamma is not required for E2-induced cytokine and 
      NO production in L. mexicana-infected macrophages from female C57BL/6 mice but it 
      may be involved in parasite clearance from these cells.
FAU - Lezama-Davila, Claudio M
AU  - Lezama-Davila CM
AD  - Department of Microbiology, The Ohio State University, Columbus, OH 43210, USA. 
      lezama-davila.1@osu.edu
FAU - Isaac-Marquez, Angelica P
AU  - Isaac-Marquez AP
FAU - Barbi, Joseph
AU  - Barbi J
FAU - Cummings, Hannah E
AU  - Cummings HE
FAU - Lu, Bao
AU  - Lu B
FAU - Satoskar, Abhay R
AU  - Satoskar AR
LA  - eng
GR  - R01 AI051823/AI/NIAID NIH HHS/United States
GR  - R01 AI51823/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080610
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (Estrogens)
RN  - 0 (Interleukin-6)
RN  - 0 (Isoenzymes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 187348-17-0 (Interleukin-12)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 4TI98Z838E (Estradiol)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.1.137 (Class Ib Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.1.153 (Pik3cg protein, mouse)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells
MH  - Class Ib Phosphatidylinositol 3-Kinase
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Estradiol/*pharmacology
MH  - Estrogens/*pharmacology
MH  - Female
MH  - Flow Cytometry
MH  - Interferon-gamma/metabolism
MH  - Interleukin-12/metabolism
MH  - Interleukin-6/metabolism
MH  - Isoenzymes/physiology
MH  - Leishmania mexicana/*drug effects
MH  - Macrophages/*parasitology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide/metabolism
MH  - Phosphatidylinositol 3-Kinases/*physiology
MH  - Sex Factors
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2008/06/11 09:00
MHDA- 2008/10/22 09:00
CRDT- 2008/06/11 09:00
PHST- 2008/06/11 09:00 [pubmed]
PHST- 2008/10/22 09:00 [medline]
PHST- 2008/06/11 09:00 [entrez]
AID - icb200839 [pii]
AID - 10.1038/icb.2008.39 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2008 Aug-Sep;86(6):539-43. doi: 10.1038/icb.2008.39. Epub 2008 
      Jun 10.