PMID- 22001991
OWN - NLM
STAT- MEDLINE
DCOM- 20120210
LR  - 20200106
IS  - 2299-5684 (Electronic)
IS  - 1734-1140 (Linking)
VI  - 63
IP  - 4
DP  - 2011
TI  - Anti-inflammatory effects of LASSBio-998, a new drug candidate designed to be a 
      p38 MAPK inhibitor, in an experimental model of acute lung inflammation.
PG  - 1029-39
AB  - We investigated the effects of LASSBio-998 (L-998), a compound designed to be a 
      p38 MAPK (mitogen-activated protein kinase) inhibitor, on lipopolysaccharide 
      (LPS)-induced acute lung inflammation in vivo. BALB/c mice were challenged with 
      aerosolized LPS inhalation (0.5 mg/ml) 4 h after oral administration of L-998. 
      Three hours after LPS inhalation, bronchoalveolar lavage fluid was obtained to 
      measure the levels of the proinflammatory cytokines TNF-alpha (tumor necrosis 
      factor-alpha) and IL-1 (interleukin-1) and the chemokines MCP-1 (monocyte 
      chemoattractant protein-1) and KC (keratinocyte chemoattractant). In addition, 
      neutrophil infiltration and p38 MAPK phosphorylation was measured. L-998 
      inhibited LPS-induced production of TNF-alpha and IL-1beta and did not alter KC and 
      MCP-1 levels. Furthermore, L-998 also significantly decreased neutrophil 
      accumulation in lung tissues. As expected, L-998 diminished p38 MAPK 
      phosphorylation and reduced acute lung inflammation. Inhibition of p38 MAPK 
      phosphorylation by L-998 was also demonstrated in LPS-challenged murine C57BL/6 
      peritoneal macrophages in vitro, with concentration-dependent effects. L-998 
      suppressed LPS-induced lung inflammation, most likely by inhibition of the 
      cytokine-p38 MAPK pathway, and we postulate that L-998 could be a clinically 
      relevant anti-inflammatory drug candidate.
FAU - Brando Lima, Aline C
AU  - Brando Lima AC
AD  - Laboratory of Cellular Immunopharmacology, Institute of Medical Biochemistry, 
      Federal University of Rio de Janeiro, CCS, 21941-902, Rio de Janeiro, Brazil.
FAU - Machado, Alexandre L
AU  - Machado AL
FAU - Simon, Patricia
AU  - Simon P
FAU - Cavalcante, Moises M
AU  - Cavalcante MM
FAU - Rezende, Daniele C
AU  - Rezende DC
FAU - Sperandio da Silva, Gilberto M
AU  - Sperandio da Silva GM
FAU - Nascimento, Paulo Gustavo B D
AU  - Nascimento PG
FAU - Quintas, Luis E M
AU  - Quintas LE
FAU - Cunha, Fernando Q
AU  - Cunha FQ
FAU - Barreiro, Eliezer J
AU  - Barreiro EJ
FAU - Lima, Lidia M
AU  - Lima LM
FAU - Koatz, Vera L G
AU  - Koatz VL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Pharmacol Rep
JT  - Pharmacological reports : PR
JID - 101234999
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Quinolines)
RN  - 0 (ethyl 6-cyclohexylurea-(1,3)dioxolo(5,4-g)quinoline-7-carboxylate)
RN  - 8W8T17847W (Urea)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/administration & dosage/*pharmacology
MH  - Bronchoalveolar Lavage Fluid
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - In Vitro Techniques
MH  - Inflammation/*drug therapy/pathology
MH  - Inflammation Mediators/metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Lung/drug effects/pathology
MH  - Macrophages, Peritoneal/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Neutrophils/drug effects/metabolism
MH  - Phosphorylation/drug effects
MH  - Quinolines/administration & dosage/*pharmacology
MH  - Urea/administration & dosage/*pharmacology
MH  - p38 Mitogen-Activated Protein Kinases/*antagonists & inhibitors
EDAT- 2011/10/18 06:00
MHDA- 2012/02/11 06:00
CRDT- 2011/10/18 06:00
PHST- 2010/10/24 00:00 [received]
PHST- 2011/04/14 00:00 [revised]
PHST- 2011/10/18 06:00 [entrez]
PHST- 2011/10/18 06:00 [pubmed]
PHST- 2012/02/11 06:00 [medline]
AID - S1734-1140(11)70619-3 [pii]
AID - 10.1016/s1734-1140(11)70619-3 [doi]
PST - ppublish
SO  - Pharmacol Rep. 2011;63(4):1029-39. doi: 10.1016/s1734-1140(11)70619-3.