Preventive/remedy for respiratory diseases
It is intended to provide a compound inhibiting the activity of a protein having an amino acid sequence which is the same or substantially the same as one of the amino acid sequences represented by SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62 and so on, or its salt; a compound inhibiting the expression of a gene of the above protein; an antisense nucleotide containing a base sequence which is complementary or substantially complementary to the base sequence of a DNA encoding the above protein or its partial peptide or a part of the base sequence; an antibody against the above protein or its partial peptide; and so on. The above compound, antisense nucleotide, antibody and so on are usable as a prophylactic/therapeutic agent for respiratory diseases, etc.
1. A method of screening for a potential prophylactic/therapeutic agent for respiratory diseases, which comprises:
(i) culturing a cell expressing a protein in the presence and absence of a test compound and measuring cholesterol hydroxylation activity of the protein, wherein the protein comprises (a) the amino acid sequence of SEQ ID NO: 2 or (b) an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 2 and having cholesterol hydroxylation activity, or a salt thereof;
(ii) comparing the measured cholesterol hydroxylation activity of the protein in the presence of the test compound with the measured activity of the protein in the absence of the test compound;
(iii) selecting the test compound which decreases cholesterol hydroxylation activity of the protein by at least 20%;
(iv) measuring and comparing the production of inflammatory cytokines in the presence and absence of the test compound selected in step (iii); and
(v) selecting the test compound which decreases the production of inflammatory cytokines as the prophylactic/therapeutic agent for respiratory diseases.
2. The screening method according to claim 1 , wherein said protein comprises the amino acid sequence represented of SEQ ID NO: 2 or a salt thereof.
3. The method according to claim 1 , wherein said respiratory disease is chronic obstructive pulmonary disease.