TLR7 stimulation induced type I and III IFN in HBECs.

<p>Graphs depict IFN-β protein [A], IFN-β mRNA [B], IFN-λ protein [C], IFN-λ1 mRNA [D] and IFN-λ2/3 mRNA [E] at 24 h following stimulation with R848. Squares represent asthmatics, circles represent non-asthmatics. * = p<0.05, ** = p<0.01, *** = p<0.001.</p

IL-8 induction following TLR stimulation in HBECs.

<p>Graphs depict IL-8 production at 8 h following stimulation with Poly I:C [A], CpG-C-ODN [B], CpG-B-ODN [C] and RNA40 [D] and at 24 h following R848 [E] and LPS [F]. Squares represent asthmatics, circles represent non-asthmatics. * = p<0.05, ** = p<0.01, *** = p<0.001.</p

TLR7 stimulation induced type I but not type III IFN in PBMCs.

<p>Graphs depict IFN-α protein production 8 h [A], 24 h [B] and 48 h [C] and IFN-β protein at 8 h [D], 24 h [E] and 48 h [F] post R848 stimulation. Squares represent asthmatics, circles represent non-asthmatics. * = p<0.05, ** = p<0.01, *** = p<0.001.</p

IL-8 induction following TLR stimulation in PBMCs.

<p>Graphs depict IL-8 production at 8 h following stimulation with PIC [A], R848 [B], LPS [C] and RNA40 [D], 24 h following PIC [E], R848 [F], CpG-C-ODN [G], CpG-B-ODN [H], LPS [I] and RNA40 [J] and 48 h following PIC [K]. Squares represent asthmatics, circles represent non-asthmatics. * = p<0.05, ** = p<0.01, *** = p<0.001.</p

IL-6 induction following TLR stimulation in PBMCs.

<p>Graphs depict IL-6 production at 8 h following stimulation with PIC [A], R848 [D], LPS [G] and LPS [K], 24 h following PIC [B], R848 [E], LPS [H] and LPS [L] and 48 h following PIC [C], R848 [F], LPS [J] and LPS [M]. Squares represent asthmatics, circles represent non-asthmatics. * = p<0.05, ** = p<0.01, *** = p<0.001.</p

TLR3 induced type I and III IFN in HBECs.

<p>Figures depict IFN-β protein [A], IFN-β mRNA [B], IFN-λ protein [C], IFN-λ1 mRNA [D] and IFN-λ2/3 mRNA [E] at 8 h following Poly I:C stimulation. Squares represent asthmatics and circles represent non-asthmatics. * = p<0.05, ** = p<0.01, *** = p<0.001.</p

Additional file 1: of Healthcare resource use and costs of multiple sclerosis patients in Germany before and during fampridine treatment

MS-related healthcare resource use before and during fampridine treatment. Description of data: The additional file includes an overview of the MS-related healthcare resource use in the pre- and post-index period in a tabular format. (DOCX 17 kb

Cool-temperature-mediated activation of phospholipase C-[gamma]2 in the human hereditary disease PLAID

Deletions in the gene encoding signal-transducing inositol phospholipid-specific phospholipase C-[gamma]2 (PLC[gamma]2) are associated with the novel human hereditary disease PLAID (PLC[gamma]2-associated antibody deficiency and immune dysregulation). PLAID is characterized by a rather puzzling concurrence of augmented and diminished functions of the immune system, such as cold urticaria triggered by only minimal decreases in temperature, autoimmunity, and immunodeficiency. Understanding of the functional effects of the genomic alterations at the level of the affected enzyme, PLC[gamma]2, is currently lacking. PLC[gamma]2 is critically involved in coupling various cell surface receptors to regulation of important functions of immune cells such as mast cells, B cells, monocytes/macrophages, and neutrophils. PLC[gamma]2 is unique by carrying three Src (SH) and one split pleckstrin homology domain (spPH) between the two catalytic subdomains (spPHn-SH2n-SH2c-SH3-spPHc). Prevailing evidence suggests that activation of PLC[gamma]2 is primarily due to loss of SH-region-mediated autoinhibition and/or enhanced plasma membrane translocation. Here, we show that the two PLAID PLC[gamma]2 mutants lacking portions of the SH region are strongly (> 100-fold), rapidly, and reversibly activated by cooling by only a few degrees. We found that the mechanism(s) underlying PLC[gamma]2 PLAID mutant activation by cool temperatures is distinct from a mere loss of SH-region-mediated autoinhibition and dependent on both the integrity and the pliability of the spPH domain. The results suggest a new mechanism of PLC[gamma] activation with unique thermodynamic features and assign a novel regulatory role to its spPH domain. Involvement of this mechanism in other human disease states associated with cooling such as exertional asthma and certain acute coronary events appears an intriguing possibility