Crohn's Disease (CD) afflicts over half a million Americans with an annual economic impact exceeding $10 billion. Granulocyte macrophage colony-stimulating factor (GM-CSF) can increase patient immune responses against intestinal microbes that promote CD and has been effective for some patients in clinical trials. We have made important progress toward developing GM-CSF variants that could be mo...

The human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor consists of 2 glycoprotein subunits, GMRalpha and GMRbeta. GMRalpha in isolation binds to GM-CSF with low affinity. GMRbeta does not bind GM-CSF by itself, but forms a high-affinity receptor in association with GMRalpha. Previously, it was found that N-glycosylation of GMRalpha is essential for ligand binding. The pres...

BACKGROUND & AIMS Crohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects. METHODS We performed exome sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls). To validate ...

Interleukin-7 (IL-7) is an important growth factor in B and T lymphopoiesis in mouse and human, whereas IL-7 has been regarded to lack proliferative effects on cells within the myeloid lineage. However, we have recently reported that IL-7 potently can enhance colony stimulating factor (CSF)-induced myelopoiesis from primitive murine hematopoietic progenitors, showing a novel role of IL-7 in ear...

The cell lines FDC-Pl and 32D cl-23 have previously been used as unique indicators for the growth-promoting activity of interleukin-3. We show that FDC-Pl cells respond to granulocyte/macrophage colony-stimulating factor (GM-CSF, CSF-2) as well as to interleukin-3. In keeping with this finding, FDC-Pl cells express the macrophage-specific marker, F4/80. FDC-Pl cells do not, however, respond to ...

The granulocyte macrophage colony-stimulating factor (GM-CSF) is known to play a protective role in intestinal inflammation. However, the effects of GM-CSF on the progression of colitis to colorectal carcinoma have long remained unclear. We have recently demonstrated that GM-CSF produced by colonic epithelial cells promotes colorectal tumorigenesis by stimulating the secretion of vascular endot...

Suramin and suramin analogues strongly inhibit both nucleotide interaction with the nucleotide-binding site of granulocyte-macrophage colony-stimulating factor (GM-CSF) and bioactivity of the molecule as assessed by competition photoaffinity labeling and cell proliferation assay, respectively. The half-maximal inhibition of cell proliferation by suramin occurs at 68 +/- 2.5 microM; three surami...