Breast tumors infiltrated by matrix metalloprotease 11 (MMP-11)+ mononuclear inflammatory cells are prone to form metastases; express high levels of interleukin (IL)-1, IL-5, IL-6, IL-17, interferon β (IFNβ) and NFκB; and exhibit an increased CD68+/(CD3+CD20+) cell ratio at their invasive front. These factors, which are implicated in the crosstalk between tumors and their inflammatory microenvi...

Activation of Tyk2 and Stat3 is required for the Apoptotic Actions of IFNβ in Primary Pro-B cells. Ana M. Gamero, Ramesh Potla, Joanna Wegrzyn, Magdelena Szelag, Andrea E. Edling, Kazuya Shimoda, Daniel C. Link, Jozef Dulak, Darren P. Baker, Yoshinari Tanabe, Jason M. Grayson, and Andrew C. Larner 1 Laboratory of Experimental Immunology, National Cancer Institute-Frederick, MD 21702; Department...

In several preclinical tumor models, antitumor effects occur after intratumoral electroporation, also known as electrotransfer, of plasmid DNA devoid of a therapeutic gene. In mouse melanomas, these effects are preceded by significant elevation of several proinflammatory cytokines. These observations implicate the binding and activation of intracellular DNA-specific pattern recognition receptor...

Type I interferons (IFNs) activate differential cellular responses through a shared cell surface receptor composed of the two subunits, IFNAR1 and IFNAR2. We propose here a mechanistic model for how IFN receptor plasticity is regulated on the level of receptor dimerization. Quantitative single-molecule imaging of receptor assembly in the plasma membrane of living cells clearly identified IFN-in...

Streptococcus pneumoniae infection is a leading cause of bacterial pneumonia, sepsis and meningitis and is associated with high morbidity and mortality. Type I interferon (IFN-I), whose contribution to antiviral and intracellular bacterial immunity is well established, is also elicited during pneumococcal infection, yet its functional significance is not well defined. Here, we show that IFN-I p...

PUM1 is an RNA binding protein shown to regulate the stability and function of mRNAs bearing a specific sequence. We report the following: (i) A key function of PUM1 is that of a repressor of key innate immunity genes by repressing the expression of LGP2. Thus, between 12 and 48 hours after transfection of human cells with siPUM1 RNA there was an initial (phase 1) upsurge of transcripts encodin...

The interferons λ (IFNsλ), also known as IL-28 and IL-29, are co-expressed with IFNβ following Toll Like Receptor (TLR) stimulation in human monocyte-derived dendritic cells (DCs). IFNλ shares with type I IFNs an intracellular signaling pathway which drives the expression of a common set of gene. However, IFNλ signaling is initiated through a membrane receptor system distinct from that of type ...

Natural killer (NK) cells play an important role in the defense against viral infections. Activation of resting NK cells is tightly controlled by the balance of surface inhibitory and activating receptors and aided by cytokines released by accessory cells along the anti-viral response. On the other hand, NK cells express functional pattern recognition receptors (PRRs) whose function has been mo...

Nucleus accumbens-associated protein 1 (NAC1), a transcriptional co-regulator, is overexpressed in advanced prostate cancer. However, the NAC1-regulated transcriptome has not been completely explored. In the present study, the functional silencing of NAC1 blocked the migration of prostate cancer cells and suppress osteoclastogenesis. The present study also determined that NAC1 was overexpressed...

AIMS The phase 3 TRANSFORMS and FREEDOMS studies established the efficacy of fingolimod in reducing multiple sclerosis (MS) relapses and magnetic resonance imaging lesions compared with intramuscular (IM) interferon (IFN) β-1a and placebo over 12 and 24 months, respectively. METHODS To investigate the efficacy of fingolimod at the approved 0.5 mg dose in patients early in the MS disease cours...