Mark Cunningham
Janssen Pharmaceutica
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Mark Cunningham.
American Journal of Respiratory and Critical Care Medicine | 2008
Lynne A. Murray; Darryl A. Knight; Laura McAlonan; Rochelle L. Argentieri; Amrita Joshi; Furquan Shaheen; Mark Cunningham; Lena Alexopolou; Richard A. Flavell; Robert T. Sarisky; Cory M. Hogaboam
RATIONALE Acute respiratory distress syndrome (ARDS) manifests clinically as a consequence of septic and/or traumatic injury in the lung. Oxygen therapy remains a major therapeutic intervention in ARDS, but this can contribute further to lung damage. Patients with ARDS are highly susceptible to viral infection and it may be due to altered Toll-like receptor (TLR) expression. OBJECTIVES To evaluate the role of TLR3 in ARDS. METHODS TLR3 expression and signaling was determined in airway epithelial cells after in vitro hyperoxia challenge. Using a murine model of hyperoxia-induced lung injury, the role of TLR3 was determined using either TLR3-gene deficient mice or a specific neutralizing antibody directed to TLR3. MEASUREMENTS AND MAIN RESULTS Increased TLR3 expression was observed in airway epithelial cells from patients with ARDS. Further, hyperoxic conditions alone were a major stimulus for increased TLR3 expression and activation in cultured human epithelial cells. Interestingly, TLR3(-/-) mice exhibited less acute lung injury, activation of apoptotic cascades, and extracellular matrix deposition after 5 days of 80% oxygen compared with wild-type (TLR3(+/+)) mice under the same conditions. Administration of a monoclonal anti-TLR3 antibody to TLR3(+/+) mice exposed to hyperoxic conditions likewise protected these mice from lung injury and inflammation. CONCLUSIONS The potential for redundancy in function as well as cross-talk between distinct TLRs may indeed contribute to whether the inflammatory cascade can be effectively disrupted once signaling has been initiated. Together, these data show that TLR3 has a major role in the development of ARDS-like pathology in the absence of a viral pathogen.
Viral Immunology | 2008
Katherine S. Held; William G. Glass; Yevgeniya I. Orlovsky; Kimberly Shamberger; Ted Petley; Patrick Branigan; Jill Carton; Heena Beck; Mark Cunningham; Jacqueline Benson; Thomas E. Lane
The functional role of IL-12 and IL-23 in host defense and disease following viral infection of the CNS was determined. Instillation of mouse hepatitis virus (MHV, a positive-strand RNA virus) into the CNS of mice results in acute encephalitis followed by a chronic immune-mediated demyelinating disease. Antibody-mediated blocking of either IL-23 (anti-IL-23p19) or IL-12 and IL-23 (anti-IL-12/23p40) signaling did not mute T-cell trafficking into the CNS or antiviral effector responses and mice were able to control viral replication within the brain. Therapeutic administration of either anti-IL-23p19 or anti-IL-12/23p40 to mice with viral-induced demyelination did not attenuate T-cell or macrophage infiltration into the CNS nor improve clinical disease or diminish white matter damage. In contrast, treatment of mice with anti-IL-12/23p40 or anti-IL-23p19 resulted in inhibition of the autoimmune model of demyelination, experimental autoimmune encephalomyelitis (EAE). These data indicate that (1) IL-12 and IL-23 signaling are dispensable in generating a protective T-cell response following CNS infection with MHV, and (2) IL-12 and IL-23 do not contribute to demyelination in a model independent of autoimmune T-cell-mediated pathology. Therefore, therapeutic targeting of IL-12 and/or IL-23 for the treatment of autoimmune diseases may offer unique advantages by reducing disease severity without muting protective responses following viral infection.
Archive | 2006
Jacqueline Benson; Mark Cunningham; Cynthia Duchala; Jill Giles-Komar; Jinquan Luo; Michael Rycyzyn; Raymond Sweet
Archive | 2006
Jacqueline Benson; Jill Carton; Mark Cunningham; Yevgeniya I. Orlovsky; Robert Rauchenberger; Raymond Sweet
Archive | 2004
Jacqueline Benson; Mark Cunningham
Archive | 2009
Mark Cunningham; Yiqing Feng; Katharine Heeringa; Jinquan Luo; Robert Rauchenberger; Mark Rutz; Lani San Mateo; Robert T. Sarisky; Raymond Sweet; Fang Teng; Alexey Teplyakov; Sheng-Jiun Wu
Archive | 2011
Jacqueline Benson; Jill Carton; Mark Cunningham; Yevgeniya I. Orlovsky; Robert Rauchenberger; Raymond Sweet
Archive | 2006
Karen E. Duffy; Mark Cunningham; Mouhamadou L. Mbow; Robert T. Sarisky
Archive | 2013
Mark Cunningham; Yiqing Feng; Katharine Heeringa; Jinquan Luo; Robert Rauchenberger; Mark Rutz; Lani San Mateo; Robert T. Sarisky; Raymond Sweet; Fang Teng; Alexey Teplyakov; Sheng-Jiun Wu
Archive | 2013
Mark Cunningham; Yiqing Feng; Katharine Heeringa; Jinquan Luo; Robert Rauchenberger; Mark Rutz; Lani San Mateo; Robert T. Sarisky; Raymond Sweet; Fang Teng; Alexey Teplyakov; Sheng-Jiun Wu