INFECTIOUS DISEASE: Targeting tissue destruction in tuberculosis

Infection with the bacterium Mycobacterium tuberculosis can cause tuberculosis. In most people, however, the bacteria do not cause disease but are sequestered in the lung in walled off compartments known as granulomas. By studying both human samples and mice expressing the human form of the protein MMP-1, a team of researchers, led by Paul Elkington, at Imperial College London, United Kingdom, has now generated data indicating that MMP-1 drives lung tissue destruction in granulomas. The team therefore suggests that targeting MMP-1 might provide a way to limit the damage caused by infection with Mycobacterium tuberculosis. This and other data indicating that MMPs represent viable therapeutic targets to control Mycobacterium tuberculosis infections are discussed in an accompanying commentary by Padmini Salgame, at the University of Medicine and Dentistry of New Jersey, Newark.

TITLE: MMP-1 drives immunopathology in human tuberculosis and transgenic mice

ACCOMPANYING COMMENTARY TITLE: MMPs in tuberculosis: granuloma creators and tissue destroyers

ONCOLOGY: On the origin of the tumor

It is, in general, very hard to cure a cancer once it has become clinically apparent. By identifying the cells from which a cancer arises researchers hope that it might be possible to detect cancerous lesions at much earlier stages and treat them more successfully. With this in mind, Andrzej Dlugosz and colleagues, at the University of Michigan Medical School, Ann Arbor, have now identified in mice the cells from which two forms of basal cell carcinoma arise.

Basal cell carcinomas are the most common human cancers. Although uncontrolled Hedgehog signaling drives almost all basal cell carcinomas, it is not clear why they differ in appearance and can be divided into different types. In this study, Dlugosz and colleagues used engineered mouse models of basal cell carcinoma to determine that superficial basal cell carcinoma-like tumors arise from interfollicular epidermis and nodular basal cell carcinoma-like tumors from hair follicle stem cells, thereby generating data that indicate that the cell of origin influences the type of basal cell carcinoma that develops.

In an accompanying commentary, Ervin Epstein Jr., at Children's Hospital of Oakland Research Institute, Oakland, discusses how these data fit with other recent studies on the origin of basal cell carcinomas and open doors for further investigation.

TITLE: Basal cell carcinomas in mice arise from hair follicle stem cells and multiple epithelial progenitor populations

ACCOMPANYING COMMENTARY TITLE: Mommy - where do tumors come from?

INFLAMMATION: New role for energy generators in controlling inflammation

The inflammatory response is initiated as a protective response but if the response is sustained or excessive it leads to tissue damage. A team of researchers, led by Jahar Bhattacharya, at Columbia University College of Physicians and Surgeons, New York, has now identified in mice a new molecular mechanism that curbs excessive inflammation. Specifically, the team found that mitochondria (the energy generating compartments of a cell) in cells lining blood vessels in the lungs are key regulators of inflammation. As highlighted by both the authors and, in an accompanying commentary, Laura A. Dada and Jacob I. Sznajder, these data provide potential new therapeutic targets for the treatment of the deleterious effects of the inflammatory response.

TITLE: Activation of TNFR1 ectodomain shedding by mitochondrial Ca2+ determines the severity of inflammation in mouse lung microvessels

ACCOMPANYING COMMENTARY TITLE: Mitochondrial Ca2+ and ROS take center stage to orchestrate TNF-alpha-mediated inflammatory responses

GASTROENTEROLOGY: Cellular connection between inflammatory bowel disease and colon cancers

Individuals with the inflammatory bowel disease ulcerative colitis are at high risk for developing colon cancer, but the mechanisms underlying this are not completely understood. A team of researchers, led by Stefan Fichtner-Feigl, at the University of Regensburg, Germany, has now identified a defined population of immune cells known as macrophages that facilitate the development of colon cancer in a mouse model of ulcerative colitis. These cells were marked by expression of F4/80, high levels of CD11b, and low levels of Gr1 and promoted tumor development, in part, via the production of the tumor-promoting factors IL-6 and TGF-beta-1. The authors plan to investigate whether individuals with ulcerative colitis also have increased numbers of these macrophages and whether their presence can be used to predict the development of colon cancer.

TITLE: Tumor development in murine ulcerative colitis depends on MyD88 signaling of colonic F4/80+CD11bhighGr1low macrophages

Source:
Karen Honey
Journal of Clinical Investigation