JCI online early table of contents: Nov. 9, 2009

November 09, 2009

EDITOR'S PICK: NSAIDs prevent early sign of Alzheimer disease in mice

If taking nonsteroidal antiinflammatory drugs (NSAIDs) such as ibuprofen or naproxen is to protect you from developing Alzheimer disease then you will have to start taking them at a very early age according to research in a mouse model of the disease.

Emerging data indicate that an early molecular event in the development of Alzheimer disease is the induction of neuronal cell cycle events (CCEs). While searching for triggers of neuronal CCEs, a team of researchers led by Karl Herrup, at The State University of New Jersey, Piscataway, and Bruce Lamb, at the Cleveland Clinic, Cleveland, developed two lines of experimental evidence implicating a role for neuroinflammation in the process in a mouse model of Alzheimer disease. First, administration of the inflammatory molecule LPS induced the early appearance of neuronal CCEs. Second, treatment with either ibuprofen or naproxen blocked the induction of neuronal CCEs. Importantly, although no new neuronal CCEs were induced when older mice were treated with either of these NSAIDs, existing neuronal CCEs persisted. These data provide a potential explanation for observations in humans: retrospective studies indicate long-term NSAID use is protective against AD, whereas prospective NSAID clinical trials have been unsuccessful in patients with mild to moderate AD.TITLE: NSAIDs prevent, but do not reverse, neuronal cell cycle reentry in a mouse model of Alzheimer disease


Karl Herrup
The State University of New Jersey, Piscataway, New Jersey, USA.
Phone: (732) 445-1794; Fax: (732) 445-3306; E-mail: herrup@biology.rutgers.edu.

Bruce T. Lamb
Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Phone: (216) 444-3592; Fax: (216) 444-7927; E-mail: lambb@ccf.org.

View this article at: http://www.jci.org/articles/view/39716?key=FZ0P005I36nTaBOsg7d1

EDITOR'S PICK: Targeting PKC-theta protein: a way to inhibit harmful immune responses?

For some individuals with leukemia, the best treatment option is to receive a bone marrow transplant from a person who is not an identical genetic match. The donor bone marrow gives rise to immune cells that attack the leukemia (a response known as a graft-versus leukemia [GVL] response). In some cases, however, the immune cells generated by the donor bone marrow attack other cells in the patient's body and this highly toxic response is known as graft-versus-host disease (GVHD). Much research is being conducted to identify drugs that can prevent GVHD but preserve GVL responses and responses against infectious agents. A team of researchers, led by Amer Beg and Xue-Zhong Yu, at the H. Lee Moffitt Cancer Center and Research Institute, Tampa, has now identified the protein PKC-theta as a potential drug target in this context by determining that it is required in mice for GVHD induction but not for GVL or protective responses to infectious agents.TITLE: PKC-theta is required for alloreactivity and GVHD but not for immune responses toward leukemia and infection in mice


Amer A. Beg
H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Phone: (813) 745-5714; Fax: (813) 979-7265; E-mail: amer.beg@moffitt.org.

Xue-Zhong Yu
H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Phone: (813) 745-3562; Fax: (813) 979-7265; E-mail: xue.yu@moffitt.org.

View this article at: http://www.jci.org/articles/view/39692?key=zd7vNZFNtFlFYjT9Mfn6

EDITOR'S PICK: Interstitial macrophages: immune cells that prevent asthma

Microbe-derived molecules able to stimulate the immune system are omnipresent in the air, and the presence of one such molecule (LPS) promotes asthma in some individuals. What prevents inhalation of LPS from promoting asthma in the majority of individuals is not well understood. However, Fabrice Bureau and colleagues, at the University of Liège, Belgium, have now ascribed this function in mice to a population of lung immune cells known as lung interstitial macrophages (IMs). Surprisingly, this is the first in vivo function described for these cells.

The way in which airborne LPS promotes asthma is by inducing lung immune cells known as DCs to initiate Th2 immune responses towards normally innocuous allergens. In the study, mouse IMs were found to produce high levels of the soluble immune factor IL-10, to inhibit LPS-induced DC activation in an IL-10-dependent manner, and to prevent the induction of Th2 responses directed towards innocuous allergens following exposure to LPS and the allergen. Importantly, mice in which IMs had been depleted developed severe asthmatic reactions to innocuous airborne allergens inhaled with low doses of LPS. The authors therefore conclude that IMs help prevent airborne LPS from promoting allergy in mice and suggest that they might have a similar function in humans; determining whether inhibition or dysfunction of IMs contributes to the development of asthma in humans is likely to be an area of future investigation.TITLE: Lung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice


Fabrice Bureau
University of Liège, Liège, Belgium.
Phone: 32-4-366-42-84; Fax: 32-4-366-42-85; E-mail: fabrice.bureau@ulg.ac.be.

View this article at: http://www.jci.org/articles/view/39717?key=ilz1n88N1gsZL8Ogbs3d

DERMATOLOGY: Antagonizing the male hormone receptor accelerates wound healing

TITLE: Monocyte/macrophage androgen receptor suppresses cutaneous wound healing in mice by enhancing local TNF-alpha expression


Chawnshang Chang
University of Rochester Medical Center, Rochester, New York, USA.
Phone: (585) 273-4500; Fax: (585) 756-4133; E-mail: chang@URMC.rochester.edu.

View this article at: http://www.jci.org/articles/view/39335?key=HxDBrXTd1eaignHKtA0N

METABOLISM: The proteins LEPROT and LEPROTL1 link nutritional signals to growth hormone actions

TITLE: LEPROT and LEPROTL1 cooperatively decrease hepatic growth hormone action in mice


Bernard Bailleul
INSERM U545, Institut Pasteur de Lille, Lille, France.
Phone: 33-3-20-87-71-25; Fax: 33-3-20-87-71-98; E-mail: Bernard.Bailleul@pasteur-lille.fr.

View this article at: http://www.jci.org/articles/view/34997?key=rSe47K23kACXbb0O3bcJ

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